Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Pathological processes of the LIVER.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The transference of a part of or an entire liver from one human or animal to another.
Tumors or cancer of the LIVER.
Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Repair or renewal of hepatic tissue.
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.
A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.
Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.
Glycosides of GLUCURONIC ACID formed by the reaction of URIDINE DIPHOSPHATE GLUCURONIC ACID with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and BILIRUBIN metabolism to a more water-soluble compound that can be eliminated in the URINE and BILE.
The rate dynamics in chemical or physical systems.
The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Experimentally induced tumors of the LIVER.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia.
The circulation of BLOOD through the LIVER.
A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC 1.6.2.4.
Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.
Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)
Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
A macrolide antibiotic that is similar to ERYTHROMYCIN.
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.
Excision of all or part of the liver. (Dorland, 28th ed)
Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.
A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.
A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones.
A carcinogen that is often used in experimental cancer studies.
Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.
An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.
An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
FIBROSIS of the hepatic parenchyma due to chronic excess ALCOHOL DRINKING.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.
Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.
Glycogen stored in the liver. (Dorland, 28th ed)
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
A sulfonilamide anti-infective agent.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Cytochromes of the b group that are found bound to cytoplasmic side of ENDOPLASMIC RETICULUM. They serve as electron carrier proteins for a variety of membrane-bound OXYGENASES. They are reduced by the enzyme CYTOCHROME-B(5) REDUCTASE.
A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Elements of limited time intervals, contributing to particular results or situations.
Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
A drug-metabolizing, cytochrome P-448 (P-450) enzyme which catalyzes the hydroxylation of benzopyrene to 3-hydroxybenzopyrene in the presence of reduced flavoprotein and molecular oxygen. Also acts on certain anthracene derivatives. An aspect of EC 1.14.14.1.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
Proteins prepared by recombinant DNA technology.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
INFLAMMATION of the LIVER.
A bile pigment that is a degradation product of HEME.
A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)
Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.
Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.
Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.
An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.
Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.
Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.
A drug-metabolizing enzyme found in the hepatic, placental and intestinal microsomes that metabolizes 7-alkoxycoumarin to 7-hydroxycoumarin. The enzyme is cytochrome P-450- dependent.
Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.
Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)
The relationship between the dose of an administered drug and the response of the organism to the drug.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.
Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.
A member of the BENZODIOXOLES that is a constituent of several VOLATILE OILS, notably SASSAFRAS oil. It is a precursor in the synthesis of the insecticide PIPERONYL BUTOXIDE and the drug N-methyl-3,4-methylenedioxyamphetamine (MDMA).
The measurement of an organ in volume, mass, or heaviness.
Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A short thick vein formed by union of the superior mesenteric vein and the splenic vein.
Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.
The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.
Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Treatment process involving the injection of fluid into an organ or tissue.
These compounds function as activated monosaccharide carriers in the biosynthesis of glycoproteins and oligosaccharide phospholipids. Obtained from a nucleoside diphosphate sugar and a polyisoprenyl phosphate.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.
A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.
A sympathomimetic agent with properties similar to DEXTROAMPHETAMINE. It is used in the treatment of obesity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1222)
A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.
S-Acyl coenzyme A. Fatty acid coenzyme A derivatives that are involved in the biosynthesis and oxidation of fatty acids as well as in ceramide formation.
A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.
A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.
Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.
Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Chromatographic techniques in which the mobile phase is a liquid.
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)
Hemeproteins whose characteristic mode of action involves transfer of reducing equivalents which are associated with a reversible change in oxidation state of the prosthetic group. Formally, this redox change involves a single-electron, reversible equilibrium between the Fe(II) and Fe(III) states of the central iron atom (From Enzyme Nomenclature, 1992, p539). The various cytochrome subclasses are organized by the type of HEME and by the wavelength range of their reduced alpha-absorption bands.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
A FLAVOPROTEIN oxidoreductase that occurs both as a soluble enzyme and a membrane-bound enzyme due to ALTERNATIVE SPLICING of a single mRNA. The soluble form is present mainly in ERYTHROCYTES and is involved in the reduction of METHEMOGLOBIN. The membrane-bound form of the enzyme is found primarily in the ENDOPLASMIC RETICULUM and outer mitochondrial membrane, where it participates in the desaturation of FATTY ACIDS; CHOLESTEROL biosynthesis and drug metabolism. A deficiency in the enzyme can result in METHEMOGLOBINEMIA.
Non-cadaveric providers of organs for transplant to related or non-related recipients.
A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.
Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.
Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.
Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.
Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.
An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Industrial chemicals which have become widespread environmental pollutants. Each aroclor is a mixture of chlorinated biphenyls (1200 series) or chlorinated terphenyls (5400 series) or a combination of both (4400 series).
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Phosphoric acid esters of dolichol.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A group of compounds that are derivatives of methoxybenzene and contain the general formula R-C7H7O.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis.
Mutant strain of Rattus norvegicus which is used as a disease model of kernicterus.
A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.
Single or multiple areas of PUS due to bacterial infection within the hepatic parenchyma. It can be caused by a variety of BACTERIA, local or disseminated from infections elsewhere such as in APPENDICITIS; CHOLECYSTITIS; PERITONITIS; and after LIVER TRANSPLANTATION.
Veins which drain the liver.
The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.
Established cell cultures that have the potential to propagate indefinitely.
An inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.
A benign epithelial tumor of the LIVER.
An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26.
An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)
Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.
A narcotic analgesic and antitussive. It is metabolized in the liver by ETHYLMORPHINE-N-DEMETHYLASE and used as an indicator of liver function.
INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.
Liver diseases caused by infections with PARASITES, such as tapeworms (CESTODA) and flukes (TREMATODA).
Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.

An investigation into the binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to DNA in vitro. (1/6656)

After metabolic activation the carcinogen 15,16-dihydro-11-[3H]methylcyclopenta[a]phenanthren-17-one binds to DNA in vitro, and this binding is prevented by 7,8-benzoflavone. Radioactivity cannot be removed from the DNA with organic solvents or by chromatography on Sephadex G-50, even after heat denaturation of the DNA. Enzymatic hydrolysis yields radioactive fractions, which elute from a column of Sephadex LH-20 immediately after the natural nucleosides. At least two species of reactive metabolites are involved in this bending, those with a half-life of a few hr and others with greater stability. After extraction from the aqueous incubation mixture, they could be detected in discrete polar fractions from separations of the complex metabolite mixture by high-pressure liquid chromatography. Their ability to bind to DNA decreased with time at ambient temperature, and they were rapidly deactivated by acid. 7,8-Benzolflavone acted by suppressing the formation of polar metabolites derived from enzymatic oxidation of the aromatic double bonds. The inhibitor had no effect on the enzymes hydroxylating saturated carbon; hence it is unlikely that metabolism of the methyl group is important in conversion of this carcinogen to its proximate form, although the presence of the 11-methyl group is essential for carcinogenic activity in this series.  (+info)

Decreased liver and lung drug-metabolizing activity in mice treated with Corynebacterium parvum. (2/6656)

Injections of killed suspensions of Corynebacterium parvum (i.p.) in young male mice were followed by time- and dose-dependent decreases in the drug-metabolizing activity of liver microsomes and lung homogenates. In vitro assays with model substrates [aminopyrine, aniline, p-nitroanisole, and benzo(a)pyrene] were used to quantitate drug-metabolizing activity. It is likely that such decreases in mixed function oxidases activity will act to significantly alter the pharmacokinetics of concurrently or subsequently administered drugs. The results provide a possible mechanism to explain several previously reported immunochemotherapeutic interactions.  (+info)

The direct spectrophotometric observation of benzo(a)pyrene phenol formation by liver microsomes. (3/6656)

Optical spectral repetitive scan analysis during the oxidative metabolism of benzo(a)pyrene by liver microsomal suspensions reveals the time-dependent formation of an intermediate(s) of which the visible spectra resemble those of several benzo(a)pyrene phenols. Liver microsomes from 3-methylcholanthrene-treated rats showed a greater rate of formation of the phenols than did microsomes from control animals; the rate of formation catalyzed by liver microsomes from phenobarbital-pretreated rats was intermediate. When 3-hydroxybenzo(a)pyrene was used as a standard for comparison of activity, the rates of formation of phenols were compared when measured by fluorometric, spectrophotometric, or high-pressure liquid chromatographic analytical techniques. An epoxide hydrase inhibitor, 1,1,1-trichloropropene-2,3-oxide, enhanced phenol formation regardless of the source of liver microsomes, and 7,8-benzoflavone inhibited control and 3-methylcholanthrene-induced microsomal metabolism of benzo(a)pyrene, 7,8-Benzoflavone did not effect benzo(a)pyrene metabolism by liver microsomes from phenobarbital-pretreated rats. The effect of inhibitors on the spectrophotometric assay correlates well with the results obtained from benzo(a)pyrene metabolite analysis using high-pressure liquid chromatography.  (+info)

Differences in benzo(a)pyrene metabolism between rodent liver microsomes and embryonic cells. (4/6656)

Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with a reduction of the K-region metabolites and a marked increase in 9-hydroxybenzo(a)-pyrene. These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. These results suggest that activation and detoxification of benzo(a)pyrene may be species and tissue variable, and susceptibility and resistence to malignant transformation may be predicted on induction of a fortuitous combination of intermediate metabolic steps.  (+info)

Effect of sex difference on the in vitro and in vivo metabolism of aflatoxin B1 by the rat. (5/6656)

Hepatic microsome-catalyzed metabolism of aflatoxin B1 (AFB1) to aflatoxin M1 and aflatoxin Q1 and the "metabolic activation" of AFB1 to DNA-alylating metabolite(s) were studied in normal male and female Sprague-Dawley rats, in gonadectomized animals, and in castrated males and normal females treated with testosterone. Microsomes from male animals formed 2 to 5 times more aflatoxin M1, aflatoxin Q1, and DNA-alkylating metabolite(s) than those from females. Castration reduced the metabolism of AFB1 by the microsomes from males by about 50%, whereas ovariectomy had no significant effect on AFB1 metabolism by the microsomes from females. Testosterone treatment (4 mg/rat, 3 times/week for about 6 weeks) of castrated immature males and immature females enhanced the metabolism of AFB1 by their microsomes. A sex difference in the metabolism of AFB1 by liver microsomes was also seen in other strains of rats tested: Wistar, Long-Evans, and Fischer. The activity of kidney microsomes for metabolic activation was 1 to 4% that of the liver activity and was generally lower in microsomes from male rats as compared to those from female rats of Sprague-Dawley, Wistar, and Long-Evans strains. The in vitro results obtained with hepatic microsomes correlated well with the in vivo metabolism of AFB1, in that more AFB1 became bound in vivo to hepatic DNA isolated from male rats and from a female rat treated with testosterone than that isolated from control female rats. These data suggest that the differences in hepatic AFB1 metabolism may be the underlying cause of the sex difference in toxicity and carcinogenicity of AFB1 observed in rats.  (+info)

Quantitative aspects in the assessment of liver injury. (6/6656)

Liver function data are usually difficult to use in their original form when one wishes to compare the hepatotoxic properties of several chemical substances. However, procedures are available for the conversion of liver function data into quantal responses. These permit the elaboration of dose-response lines for the substances in question, the calculation of median effective doses and the statistical analysis of differences in liver-damaging potency. These same procedures can be utilized for estimating the relative hazard involved if one compares the liver-damaging potency to the median effective dose for some other pharmacologie parameter. Alterations in hepatic triglycerides, lipid peroxidation, and the activities of various hepatic enzymes can also be quantitiated in a dose-related manner. This permits the selection of equitoxic doses required for certain comparative studies and the selection of doses in chemical interaction studies. The quantitative problems involved in low-frequency adverse reactions and the difficulty these present in the detection of liver injury in laboratory animals are discussed.  (+info)

Isolation and complete covalent structure of liver microsomal paraoxonase. (7/6656)

Paraoxonase (PON1) is a serum esterase exclusively associated with high-density lipoproteins; it might confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids in oxidized low-density lipoproteins. Here I show that rabbit liver microsomes contain a PON analogue (MsPON) and report the isolation and complete covalent structure of MsPON. In detergent-solubilized microsomes, MsPON co-purifies with the microsomal triacylglycerol transfer protein (MTP) complex. MsPON was separated from the complex and purified to homogeneity under non-denaturing conditions. Automated sequence analysis of intact MsPON and peptides obtained from enzymic and chemical cleavages led to the elucidation of the complete covalent structure of MsPON. The protein is a single polypeptide consisting of 350 residues. The sequence of rabbit liver microsomal MsPON is 60% identical with that of rabbit serum PON1, and 84% identical with the sequence predicted by a human cDNA of unknown function, designated PON3. MsPON has a hydrophobic segment at the N-terminus that might serve to anchor the protein to the microsomal membrane or to the MTP complex. Unlike in the serum enzyme, two potential N-glycan acceptor sites in MsPON are not glycosylated. An absence of N-glycans was also indicated in the rabbit liver MTP. MsPON has a single free cysteine residue at position 38 and a disulphide bond between Cys-279 and Cys-348. The microsomal enzyme lacks three residues at the N-terminus that are present in the serum protein. MsPON lacks four residues at the C-terminus that are present in the rabbit serum protein but absent from human serum PON1. On the basis of the observation that MsPON displays a high degree of similarity with serum PON1, it is proposed that MsPON might have a function related to that of PON1 in serum high-density lipoprotein complexes.  (+info)

Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations. (8/6656)

Daidzein and genistein glucuronides (DG and GG), major isoflavone metabolites, may be partly responsible for biological effects of isoflavones, such as estrogen receptor binding and natural killer cell (NK) activation or inhibition. DG and GG were synthesized using 3-methylcholanthrene-induced rat liver microsomes. The Km and Vmax for daidzein and genistein were 9.0 and 7.7 micromol/L, and 0.7 and 1.6 micromol/(mg protein. min), respectively. The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O-glucuronides. DG and GG were further purified by a Sephadex LH-20 column. DG and GG competed with the binding of 17beta-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol. The concentrations required for 50% displacement of 17beta-(3H) estradiol (CB50) were: 17beta-estradiol, 1.34 nmol/L; diethylstilbestrol, 1.46 nmol/L; daidzein, 1.6 micromol/L; DG, 14.7 micromol/L; genistein, 0.154 micromol/L; GG, 7.27 micromol/L. In human peripheral blood NK cells, genistein at <0.5 micromol/L and DG and GG at 0.1-10 micromol/L enhanced NK cell-mediated K562 cancer cell killing significantly (P < 0.05). At > 0.5 micromol/L, genistein inhibited NK cytotoxicity significantly (P < 0.05). The glucuronides only inhibited NK cytotoxicity at 50 micromol/L. Isoflavones, and especially the isoflavone glucuronides, enhanced activation of NK cells by interleukin-2 (IL-2), additively. At physiological concentrations, DG and GG were weakly estrogenic, and they activated human NK cells in nutritionally relevant concentrations in vitro, probably at a site different from IL-2 action.  (+info)

BioAssay record AID 1340971 submitted by ChEMBL: Hepatic extraction ratio in mouse liver microsomes at 1 uM in presence of NADPH by LC-MS/MS method.
TY - JOUR. T1 - Selective deficiency of debrisoquine 4-hydroxylase activity in mouse liver microsomes. AU - Masubuchi, Yasuhiro. AU - Iwasa, Takashi. AU - Hosokawa, Shin. AU - Suzuki, Tokuji. AU - Horie, Toshiharu. AU - Imaoka, Susumu. AU - Funae, Yoshihiko. AU - Narimatsu, Shizuo. PY - 1997/9. Y1 - 1997/9. N2 - Cytochrome P450 enzymes belonging to the CYP2D subfamily have been shown to be one of determinants of the polymorphic drug oxidations in the human and the rat. Debrisoquine 4-hydroxylation is a typical reaction catalyzed by these enzymes. However, various strains of mice were observed to have much lower debrisoquine 4-hydroxylase activity than Wistar rats, whereas other monooxygenase activities in mice toward bunitrolol, propranolol, imipramine and amitriptyline, which are mediated by the CYP2D enzymes in the rat, were comparable to those of the rats. Immunoblot analysis of mouse liver microsomes with an antibody raised against a rat CYP2D enzyme indicated that the mouse liver contained ...
The results obtained in the current study demonstrate that ABT-378 undergoes CYP-dependent biotransformation to three major metabolites (M-1, M-3, and M-4) as well as several minor metabolites in human liver microsomes, consistent with a previous human liver microsomal metabolism study (Kumar et al., 1999). Members of the CYP3A subfamily (CYP3A4 and CYP3A5) were found to be the enzymes responsible for the formation of all the metabolites of ABT-378. Ritonavir was found to be a very potent inhibitor of CYP3A-mediated biotransformation of ABT-378 with a very lowKi value (0.013 μM).. The high metabolic lability precludes the use of ABT-378 alone as an effective antiviral agent for the treatment of HIV infection. The potent in vitro inhibition of the metabolism of ABT-378 by ritonavir indicates that on coadministration of ritonavir with ABT-378, the former would potentially inhibit the metabolism of the latter, thereby reducing the clearance of ABT-378. This has been demonstrated to be true in a ...
female wistar hepatic microsomes female wistar rat hepatic microsomes | order female wistar hepatic microsomes female wistar rat hepatic microsomes | How to use: female
1. Guanosine 5′-[gamma-thio]triphosphate (GTP[S]), if added before GTP, blocks both Ca2+ efflux promoted by GTP and the effect of GTP on enhancement of inositol 1,4,5-triphosphate (IP3)-promoted Ca2+ release from preloaded microsomal vesicles. If, however, GTP[S] is added after GTP, it does not reverse the Ca2+ efflux promoted by GTP, nor does it inhibit IP3-promoted Ca2+ release. 2. The effect of GTP in enhancing IP3-promoted Ca2+ release is maintained after washing the microsomal vesicles free of added GTP. After this treatment, enhancement of IP3-promoted Ca2+ efflux can be observed in the absence of poly(ethylene glycol). 3. Electron microscopy shows that during GTP treatment of microsomal vesicles there is rapid production of very large vesicular structures, apparently produced by fusion of smaller vesicles. 4. Light-scattering changes are detectable during the fusion process. 5. Both Ca2+ efflux promoted by GTP and the enhancement of IP3-promoted Ca2+ release seen in the presence of GTP ...
When one wishes to scale in vitro metabolic kinetic data to in vivo clearances, the issue of nonspecific microsomal binding needs to be addressed in addition to the plasma or blood binding that is more frequently incorporated into the scaling method. It has been demonstrated that eq. 2 could be of more general utility in the prediction of clearance than either the well stirred model containing no free fraction corrections, or only the fupcorrection (Obach, 1999). Cancellation of the fup/fuinc ratios cannot be relied upon, particularly because fuinc can depend strongly on the microsomal protein concentration that one chooses to use as shown in Table 1 and by other studies (Obach, 1996,1997; Mclure et al., 2000; Venkatakrishnan at. al., 2000). If eq. 2 is to become more widely used for in vivo clearance prediction, a better understanding of how nonspecific microsomal binding depends on microsomal protein concentration and on chemical structure is required. The ultimate goal would be to predict the ...
BioAssay record AID 510137 submitted by ChEMBL: Ratio of IC50 for CYP3A4 in human liver microsomes measured immediately to IC50 for CYP3A4 in human liver microsomes measured after incubation.
1. A partially purified UDP-glucuronyltransferase was obtained by extracting rat liver microsomal preparations with Lubrol, a non-ionic detergent. 2. The soluble enzyme catalysed conjugation of both o-aminophenol and p-nitrophenol and was extremely stable when compared with untreated microsomal preparations. 3. The characteristics of the conjugation of the two phenols were found to differ with respect to pH optimum, bivalent cation requirement and Michaelis constants, suggesting that more than one enzyme is involved in the conjugation reaction.. ...
hepatic microsomes female wistar hepatic microsomes female wistar rat | order hepatic microsomes female wistar hepatic microsomes female wistar rat | How to use: hepati
There are various subcellular fractions and they include homogenate, s9, microsomes and cytosol. These products are valuable tools in drug discovery for studying the metabolism of your compounds. Human Subcellular Products InVitroCYP™ 150-Donor Human Liver Microsomes InVitroCYP™ H-Class Human Liver Microsomes InVitroCYP™ M-Class Human Liver Microsomes Human Microsomes - Other Tissues Human Liver S9
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Human liver microsomes are subcellular fractions that contain drug-metabolizing enzymes including CYP enzymes, flavin monooxygenases, and UDP glucuronyl transferases. InVitroCYP M-class microsomes are designed to exhibit moderate CYP activity, ideal for clearance and metabolite identification studies. BioreclamationIVT extensive characterization and tissue profiling process guarantees that each lot of InVitroCYP M-class microsomes will provide consistent and reproducible results for your metabolism and clearance studies.
In cell biology, microsomes are heterogenous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.[1] Microsomes can be concentrated and separated from other cellular debris by differential centrifugation. Unbroken cells, nuclei, and mitochondria sediment out at 10,000 g, whereas soluble enzymes and fragmented ER, which contains cytochrome P450 (CYP), remain in solution (g is the Earths gravitational acceleration). At 100,000 g, achieved by faster centrifuge rotation, ER sediments out of solution as a pellet but the soluble enzymes remain in the supernatant. In this way, cytochrome P450 in microsomes is concentrated and isolated. Microsomes have a reddish-brown color, due to the presence of the heme. Because of the need for a multi-part protein-system, microsomes are necessary to analyze the metabolic activity of CYPs. These CYPs are highly ...
In the obersvation of Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein by Peng WX, Wang LS, Li HD, Abd El-Aty AM, Chen GL, Zhou HH., posted in US National Library of Medicine National Institutes of Health, researchers found that Michaelis-Menten kinetic parameters were best fitted to a one-component enzyme kinetic model. The mean K(m) (micromol/l) and V(max) (micromol/g min) values (+/-S.D.) were 26.86 (10.45) and 4.76 (2.07), 53.83 (22.25) and 2.29 (1.04), 51.48 (29.32) and 2.21(0.82), for the formation rates of 7,8,4-THI, 7,3,4-THI and 6,7,4-THI, respectively. Furafylline, the CYP1A2-specific inhibitor, estrogen and monoclonal antibody raised against human CYP1A2 (MAB-1A2) substantially inhibited the formation rates of mono-hydroxylated metabolites. The IC(50) of Fur for the formation of 7,3,4-THI, 6,7,4-THI and 7,8,4-THI was 1.0, 0.9 and 0.8 micromol/l, respectively. The IC(50) of estrogen for the formation of 7,3,4-THI, ...
Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography-tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4-hydroxylation with a Ki value of 16.3 μM, and it exhibited mechanism-based inhibition of CYP2C19-catalyzed [S]-mephenytoin 4-hydroxylation (Ki, 3.7 μM; kinact, 0.102 min−1), CYP2C8-catalyzed amodiaquine N-deethylation (Ki, 10.7 μM; kinact, 0.082 min−1), and CYP3A4-catalyzed midazolam 1-hydroxylation (Ki, 23.0 μM; kinact, 0.050 min−1) in human liver microsomes. Fargesin negligibly inhibited CYP1A2-catalyzed phenacetin O-deethylation, CYP2A6-catalyzed coumarin 7-hydroxylation,
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Cytochrome P-450 (P-450) 2A6 was purified by chromatography of human liver microsomes. The final preparation was electrophoretically homogeneous and contained 16 nmol of P-450/mg of protein. The amino-terminal amino acid sequence of the protein (first 13 residues) matched that of the reported cDNA exactly. The UV-visible spectrum indicated that the isolated hemoprotein was in the low-spin form. The protein was recognized by rabbit antibodies raised against rat P-450 2A1, and a rabbit antiserum against the P-450 2A6 preparation was also prepared. With these antibodies, it was estimated that P-450 2A6 accounted for a maximum of 1% of the total P-450 present in the human liver microsomes; the level varied greater than 100-fold among the 20 samples examined. Purified P-450 2A6 catalyzed coumarin 7-hydroxylation and 7-ethoxycoumarin O-deethylation at rates similar to those measured in the human liver sample used to prepare P-450 2A6, and these two microsomal activities were strongly inhibited by the ...
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AB - Steroid glucuronidation was investigated in solubilized female rat and rabbit liver microsomes and in preparations of UDP-glucuronsyltransferase (UDPGT) activity resolved from these organelles. Solubilized rabbit liver microsomes possessed
Initial studies aimed to characterize the effect of BSA on COD glucuronidation by HLM and confirm the contributions of UGT2B4 and UGT2B7 to C6G formation. Kinetic parameters for C6G formation in HLM in the absence of BSA were similar to those reported previously by Court et al. (2003). Addition of BSA (2%) to incubations resulted in an 88% reduction in Km without an effect on Vmax. A similar effect has been reported for the glucuronidation of several other UGT2B7 substrates by HLM (Rowland et al., 2007; Kilford et al., 2009), confirming that Km or microsomal intrinsic clearance values for UGT2B7 substrates are overestimated and underestimated, respectively, by approximately an order of magnitude when HLM are used as the enzyme source in the absence of albumin supplementation.. Also consistent with previous published data (Court et al., 2003), the screening of 13 recombinant enzymes demonstrated that only UGT2B4 and UGT2B7 glucuronidated COD. In contrast to the Michaelis-Menten (or weak substrate ...
We screened thousands of compounds and identified several drugs with improved anti-MRSA activities after they undergo human liver microsomal metabolism or in presence of Cefoxitin, a known antibacterial agents which has a high MIC against MRSA F-182. We used liquid handling workstations and LC-MS based analysis to screen and characterize active agents. We further extended screening some of the hits from the screening against additional MRSA strain, one VRE and one E. coli strain for spectrum of activity and frequency of resistance. This approach can be adopted for exploring other biological activities of these library of compounds with modifications. We are in the process of exploring the mechanism of action of these interesting agents using multi-omics study consisting of metabolomics, proteomics and genomics ...
The involvement of human cytochrome P450 (CYP) 2E1 in the hydroxylation of 4-nitrophenol (4NP) to 4-nitrocatechol (4NC) has been investigated using cDNA expression and liver microsomal kinetic and inhibitor techniques. 4NP hydroxylation by human liver microsomes and cDNA-expressed human CYP2E1 exhib …
1-Chloro-2-hydroxy-3-butene (CHB) is an in vitro metabolite of 1,3-butadiene, a rodent/human carcinogen. To search for an approach detecting CHB in vivo, it is vital to obtain a full understanding of CHB metabolism. Previously, we demonstrated that CHB was bioactivated to 1-chloro-3-buten-2-one (CBO) by alcohol dehydrogenase. However, CHB metabolism by cytochrome P450s has not been reported. Thus, in the present study, CHB metabolism by rat liver microsomes was investigated. The results showed that CHB was converted to 1-chloro-3,4-epoxy-2-butanol (CEB) and CBO. 4-Methylpyrazole, a cytochrome P450 2E1-specific inhibitor, inhibited the formation of both CEB and CBO, while 1-benzylimidazole, a generic cytochrome P450 inhibitor, completely abolished the formation of CEB and CBO, suggesting that CHB metabolism was mediated by cytochrome P450s. Because the molecules have two chiral centers, CEB was detected as two stereoisomers, which were designated D-CEB and M-CEB, and were characterized as ...
Rodent skin (extrahepatic) subcellular fractions, including matching pooled IGS Sprague-Dawley rat microsomes and S9 from dermal tissue, characterized for in vitro ADME studies to test the biotransformation of transdermal xenobiotics.
Our CYP and UGT inhibition services are conducted with Corning UltraPool® HLM 150 pooled human liver microsomes, drug probe substrates and validated LC/MS/MS methods. Options include direct and time-dependent inhibition studies with flexible endpoints. Kinetic results reported include IC50, IC50 shift (dilution and non-dilution methodology), as well as KI and kinact. Assays are also available using hepatocytes or recombinant enzyme study models.. To request a study quotation call: 781.938.2546 or send a request to: [email protected] ...
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Download Free Full-Text of an article EFFECTS OF 3 - METHYL CHOLANTHEREN ON LIVER MICROSOMAL MIXED FUNCTION OXIDASE ACTIVITIES OF ACIPENSER PERSICUS
TY - JOUR. T1 - Oxygen concentrations required for reductive defluorination of halothane by rat hepatic microsomes. AU - Lind, R. C.. AU - Gandolfi, A. J.. AU - Sipes, I. G.. AU - Brown, B. R.. AU - Waters, S. J.. PY - 1986/10/22. Y1 - 1986/10/22. N2 - The free oxygen concentrations required for reductive defluorination of halothane by rat hepatic microsomes from control and phenobarbital- (PB) and polychlorinated biphenyl- (PCB) treated animals were determined. Halothane-exposed microsomes from treated rats generated measurable levels of fluoride ion after 30 min incubations with oxygen concentrations of 5% or less. Microsomes from control animals produced fluoride only if the free oxygen concentration was 2% or less. During anoxic (0% oxygen) incubations, defluorination rates of 2.10 ± 0.17, 5.55 ± 0.38, and 5.46 ± 0.30 nmol fluoride·mg protein-1·30 min-1 were observed for microsomes from control, PB, and PCB rats, respectively. Normalizing the maximal rates of defluorination to the ...
1. Cimetidine pretreatment of male Sprague-Dawley rats caused a significant increase in the specific content of total hepatic cytochrome P-450, supporting the hypothesis that this H2-receptor antagonist has monooxygenase induction effects. 2. Quantitative ultrastructural studies of liver of cimetidine-pretreated animals also supported this hypothesis in showing a significant proliferation of smooth endoplasmic reticulum. These ultrastructural changes were qualitatively similar to those produced by treatment of rats with phenobarbital, a well-characterized monooxygenase-inducing agent whose effects were studied for comparative purposes. 3. Competitive inhibition of metoprolol αhydroxylation by cimetidine in liver microsomes prepared from untreated animals (Ki = 18.8 μM) was also demonstrated. 4. These results allowed testing of the hypothesis (Burnet el al. 1986) that inhibition of a defined monooxygenase should lead to induction of the synthesis of the relevant cytochrome P-450 isozyme. 5. The ...
hepatic microsomal mixed function oxidase system의 중추인 cytochrome p-450은 주위환경, 약물, 식이 및 영양 상태에따라 활성이 변화하는것으로 알려져있다. 또한 이 효소계를 통하여 대사되는 2-acetylaminofluorene은 guinea pig를 제외한 모든 동물에서 간암을 일으키는 물질이라는것이 밝혀져서 연구의 대상이 되고있다. 최근 cholesterol은 성인병에 있어 그 원인 인자로서 중요성이 알려지고 있으며 cytochrome p-450과 b_(5)와의 연관성이 보고된바있다. 한편 인삼은 항암작용, 대사촉진, 간조직에서의 해독작용등 여러가지 기능이 보고되어 있다. 이에 저자는 cholesterol을 투여한 흰쥐에서 hepatic microsomal cytochrome p-450 및 b_(5)의 활성에대한 영향과 2-AAF의 ring-hydroxylation과 N-hydroxylation의 변화를 관찰하고, cholesterol과 인삼을 통시에 투여한 군과 비교관찰하여 다음과 같은 결론을 얻었다. 1) 정상 ...
TY - JOUR. T1 - Liver microsomes contain multiple forms of inositol 1,4,5-trisphosphate binding proteins. T2 - Identification by nitrocellulose blot overlay. AU - Ali, Nawab. AU - Agrawal, Devendra K.. PY - 1992. Y1 - 1992. N2 - A group of proteins binding to inositol 1,4,5-trisphosphate (IP3) has been identified in rat liver microsomes by a nitrocellulose blot-overlay technique. Proteins were resolved by SDS-PAGE, blotted on nitrocellulose and incubated with [32P]IP3 followed by autoradiography. Approximately eight IP3-binding polypeptides ranging Mr 23-50 kDA were present exclusively in microsomes; these were absent from plasma membrane and mitochondrial fractions. Binding of [32P]IP3 to these proteins was displaceable to a great extent by 5 μM unlabeled IP3 but not by 10 μM IP1, IP2, IP4, ATP, or GTPγS. These results suggest that liver microsomes contain multiple forms of IP3-binding proteins that can be detected by this new method.. AB - A group of proteins binding to inositol ...
Dive into the research topics of Characterization of paracetamol UDP-glucuronosyltransferase activity in human liver microsomes. Together they form a unique fingerprint. ...
Caco-2 cell lysate, and intestinal and liver microsomes derived from female humans and rats were used to compare and contrast the metabolism and disposition of raloxifene. In Caco-2 cell lysate, raloxifene 6-β-glucuronide (M1) was the main metabolite, although raloxifene 4′-β-glucuronide (M2) was formed in comparable abundance (58% versus 42%). In rat liver and intestinal microsomes, M1 represented about 76 to 86% of glucuronidated metabolites. In contrast, raloxifene 4′-β-glucuronide (M2) was the predominant metabolite in expressed UGT1A10 (96%) and human intestinal (92%) microsomes. Intrinsic clearance for M2 (CLint, M2) in human intestinal microsomes was 33- to 72-fold higher than in rat microsomes, whereas intrinsic clearance for M1 (CLint, M1) was 3- to 4-fold lower. Taken together, total intrinsic clearance (CLint, M1 + CLint, M2) in human intestinal microsomes was 3- to 6-fold higher than that in rat intestinal microsomes, but was similar in liver microsomes. In addition, intrinsic
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1. Paeonol, the primary active component of a traditional Chinese medicine Moutan Cortex, has a wide range of pharmacological activities. In the present study, the metabolism of paeonol by cytochrome P450s (CYPs) was investigated in human liver microsomes ...
The endocannabinoid system is important for many physiological and pathological processes, but its role in the regulation of liver cytochromes P450 (CYPs) is still unknown.We studied the influence of the endocannabinoid oleamide on rat and human liver CYPs. Oleamide was administered i.p. to rats at doses of 0.1, 1 and 10 mg/kg/day for 7 days. The content and activity of key CYPs was evaluated in rat liver microsomes. Moreover, its interactions with nuclear receptors regulating CYP genes and serum levels of their ligands (prolactin, corticosterone, and free triiodothyronine) were tested in vitro CYP inhibition assays. Decreased protein levels and metabolic activities of CYP1A2, CYP2B, and CYP2C11 along with a drop in metabolic activity of CYP2D2 were observed in animals treated with oleamide (10 mg/kg/day). The activities of CYP2C6, CYP2A, and CYP3A and the levels of hormones were not altered. In vitro, oleamide exhibited a weak inhibition of rat CYP1A2, CYP2D2, and CYP2C6. The activities of rat ...
Tirilazad mesylate (Freedox), a potent inhibitor of membrane lipid peroxidation in vitro, is under clinical development for the treatment of subarachnoid hemorrhage. In humans, tirilazad is cleared almost exclusively via hepatic elimination. Characterization of three major microsomal metabolites of tirilazad by mass spectrometry indicated that hydroxylation had occurred in the pyrrolidine ring(s) and at the 6 beta-position of the steroid domain. A role for CYP3A4 in the formation of the three major metabolites (tirilazad hydroxylase activity) was established in human liver microsomal preparations: 1) Tirilazad hydroxylation was potently inhibited by troleandomycin and ketoconazole, specific inhibitors of CYP3A4. 2) The rates of tirilazad hydroxylation within a population of 14 human livers displayed a 9-fold interindividual variation and a significant correlation (r2 = .95) between tirilazad hydroxylation and testosterone 6 beta-hydroxylation. 3) Kinetic analysis of tirilazad hydroxylase ...
Publication year 1996. Abstract The oxidative biotransformation of 1, 2-dichlorobenzene (1, 2-DCB) was investigated using hepatic microsomes from male Wistar, Fischer-344 and Sprague-Dawley (SD) rats, phenobarbital (PB)- and isoniazid (ISO) pretreated male Wistar rats and from man. In addition, microsomes from cell lines selectively expressing one cytochrome P450 (P4502E1, 1A1, 1A2, 2B6, 2C9, 2D6, 2A6 and 3A4) were used. The rate of conversion was 0.09 nmol/min/mg, protein for both Wistar and Fischer-344 rat microsomes, 0.04 for SD-microsomes and 0.14 for human microsomes. Induction of Wistar rats with isoniazid (ISO, a P4502E1 inducer) or phenobarbital (PB, a P4502B1/2 inducer) resulted in an increased conversion rate of 0.20 and 0.42 nmol/min/mg, protein, respectively. Covalent binding of radioactivity to microsomal protein was similar for Wistar, Fischer and ISO-pretreated rats (16-17% of total metabolites), whereas induction with PB resulted in an increased covalent binding of 23% of total ...
TY - JOUR. T1 - Activation of propranolol and irreversible binding to rat liver microsomes. T2 - strain differences and effects of inhibitors. AU - Masubuchi, Yasuhiro. AU - Narimatsu, Shizuo. AU - Suzuki, Tokuji. PY - 1992/2/4. Y1 - 1992/2/4. UR - http://www.scopus.com/inward/record.url?scp=0026584689&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0026584689&partnerID=8YFLogxK. U2 - 10.1016/0006-2952(92)90587-9. DO - 10.1016/0006-2952(92)90587-9. M3 - Article. C2 - 1540217. AN - SCOPUS:0026584689. VL - 43. SP - 635. EP - 637. JO - Biochemical Pharmacology. JF - Biochemical Pharmacology. SN - 0006-2952. IS - 3. ER - ...
Hepatic microsomal cytochrome P450s, which are involved in the metabolism of drugs, hormones, prostaglandins and fatty acids, change when animals develop diabetes. We studied changes in cytochrome P450 isozymes in both hepatic and renal microsomes of rats with diabetes caused by streptozocin, and co …
TY - JOUR. T1 - Identification and characterization of human cytchrome P450 (CYP) isoforms interacting with cisapride. AU - Desta, Zeruesenay. AU - Thacker, David. AU - Soukhova, Nadia. AU - Shin, Jae Gook. AU - Flockhart, David A.. PY - 1999/1/1. Y1 - 1999/1/1. N2 - Using human liver microsomes (HLMs) and recombinant CYP450s, we characterized the metabolism of cisapride and documented its inhibitory effect on CYP450s. Two cisapride enantiomers (EI and EII) were separated and fractions collected for study. HPLC chromatograms of HLM incubates of cisapride separated 3 metabolite peaks, M1-M3. The identity of M1 is consistent with norcisapride, while M2 and M3 may represent oxidative hydroxylation of the fluorophenyl ring. The formation rate of M1 and 10μM cisapride in 15 HLMs significantly correlated with the activities of CYP3A, 2C19 and 1A2. Of CYP isoform specific inhibitors tested, ketoconazole potently inhibited the formation of M1, M2 and M3. Of the 10 recombinant CYP450s tested, CYP3A4, ...
Hi Methods, I am fractionating baculovirus-infected Sf9 and Sf21 insect cells, using differential centrifugation to isolate microsomal membranes. The problem is that the microsomes (50,000 x g) are very particulate, and remain clumpy even after homogenization with hand-held glass/Teflon Potter-Elvehjem tissue grinder. Even mechanical disruption of the final microsomal pellet using a small polytron leaves clumps of unresuspended membranes that are visible by eye. The insect cell microsomes are clumpy when isolated either in solutions containing high salt (0.6 M KCl, 250 mM sucrose, 3 mM MgCl2) or low salt (10 mM NaHCO3, 0.1 mM CaCl2). The two different preparative protocols are listed below. Following centrifugation, the microsomal pellets are typically resuspended in 250 mM sucrose buffered with MOPS or histidine. Why do the microsomes clump so much? Are there solutes to add (pyrophosphate, NaI, etc) that would allow easy and complete resuspension of insect cell microsomes? Thanks, Mike Autry ...
Abstract OBJECTIVE: In order to evaluate the inhibitory effects of isoniazid on cytochrome P450 (CYP) mediated drug metabolism, the in vitro inhibitory potency and specificity as w..
Lu, A.Y.H., Kuntzman, S.W., Jacobson, M. and Conney, A.H. (1972). Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. II. Role of the cytochrome P-450 and P-448 fractions in drug and steroid hydroxylations. J. Biol. Chem. 247: 1727-1734. PMID 4401153. ...
Rat and human liver microsomes oxidized ranitidine to its N−oxide(66−76%)and S−oxide(13−18%)and desmethylranitidine(12−16%).N− and S−oxidations of ranitidine were inhibited by metimazole [flavin−containing monooxygenase(FMO)inhibitor] to 96−97% and 71−85%, respectively, and desmethylation of ranitidine was inhibited by SKF525A [cytochrome P450(CYP)inhibitor] by 71−95%.Recombinant FMO isozymes like FMO1, FMO2, FMO3 and FMO5 produced 39, 79, 2180 and 4 ranitinine N−oxide and 45, 0, 580 and 280 ranitinine S−oxide pmol·min,SUP,-1,/SUP,·nmol,SUP,-1,/SUP, FMO, respectively.Desmethyranitinine was not produced by recombinant FMOs.Production of desmethylranitidine by rat and human liver microsomes was inhibited by tranylcypromine, α−naphthoflavon and quinidine, which are known to inhibit CYP2C19, 1A2 and 2D6, repectively.FMO3, the major form in adult liver, produced both ranitidine N− and S−oxides at a 4 to 1 ratio.FMO1, expressed primarily in human kidney, was 55− ...
Sigma-Aldrich offers abstracts and full-text articles by [Ramakrishna Nirogi, Raghava Choudary Palacharla, Abdul Rasheed Mohammed, Arunkumar Manoharan, Ranjith Kumar Ponnamaneni, Gopinadh Bhyrapuneni].
Unfavorable drug metabolism is the main reason for attrition of new chemical entities and withdrawal of drugs from the market, costing pharmaceutical companies a great deal of money and time. Therefore, obtaining information about the drug metabolism of a new chemical entity via the hepatic clearance in the early stages ... read more of the drug development process is crucial in guaranteeing its success. Human-based in vitro systems, especially liver microsomes, hepatocytes and liver slices are increasingly applied in the drug development process for this purpose. The aim is to determine which of these commonly used systems is the most appropriate for predicting hepatic clearance in humans. Although there is no perfect in vitro system, primary hepatocytes and the HepaRG cell line are the most representative systems of the liver at present. However, it has to be kept in mind that besides their potential to accurately predict in vivo clearance other influencing factors that may interfere with ...
Uncontrolled cell proliferation is the hall mark of many cancers, and is typically manifested by a deregulation of the cell-division cycle. CDKs play critical roles in regulating cell cycle, apop- tosis and cell differentiation. AG-024322 is a multitargeted CDK inhibitor that has been shown to induce cancer cell apoptosis and de- monstrate significant antitumor activity in hu-man tumor xenograft models. This compound is under clinical development as an intravenous anticancer agent. AG-024322 exhibited moder-ate to high systemic clearance across preclini-cal species. In vitro metabolism in human liver microsomes and hepatocytes demonstrates that glucuronidation and oxidation represent the major metabolic pathways of AG-024322. The experiments of chemical inhibition and micro-somes containing individual CYP or UGT iso-forms revealed that CYP3A and UGT1A1 appear to predominantly mediate AG-024322 oxidation and glucuronidation, respectively. Formation kinetics of the two pathways in human liver mi-crosomes
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Drugs are eliminated from the body either as unchanged parent or as metabolite. Metabolic stability plays a major role in drug clearance, with the liver being the primary site for drug biotransformation via two major enzymatic reactions: Phase I (modifications to the molecular structure itself) and Phase II reactions (conjugation reactions). A common system for measuring hepatic metabolism in early drug discovery, restricted to Phase I reactions, uses liver microsomes, a subcellular fraction containing major drug-metabolizing enzymes, including the cytochrome P450 (CYP) family and flavin monooxygenase (FMO). ...
Goal: Uridine diphospho-glucuronosyltransferases (UGTs) are membrane-bound enzymes that catalyze the conjugation of glucuronic acid onto a varied set of xenobiotics. Horses successfully and extensively glucuronidate numerous xenobiotics, along with opioids, making UGTs an very important group of drug-metabolizing enzymes for the clearance of remedy. Recombinant enzymes have allowed researchers to characterize the metabolism of a variety of remedy. The first purpose was to clone, particular and characterize equine UGTs using remedy characterised as UGT substrates in numerous species. A secondary purpose was to characterize the in vitro metabolism of morphine in horses.. Examine design: In vitro drug metabolism look at using liver microsomes and recombinant enzyme strategies.. Animals: Liver microsomes and RNA from tissue collected from two Thoroughbred mares euthanized for various causes.. Strategies: Primarily based mostly on homology to the human UGT2B7, Four equine UGT variants have been ...
Schmoldt, A; Benthe, HF; Haberland, G (1 September 1975). "Digitoxin metabolism by rat liver microsomes". Biochemical ... Gurney, E., Myers, F.W.H. and Podmore, F. (1886). Phantasms of the Living, Vols. I and II. London: Trubner and Co.. ... However, abstaining from hallucinogenic drugs, stimulant drugs, managing stress levels, living healthily, and getting plenty of ...
CYP2C9 is involved in the formation of hydroxygliclazide in human liver microsomes and in a panel of recombinant human P450s in ... Rieutord, A; Stupans, I; Shenfield, GM; Gross, AS (1995). "Gliclazide hydroxylation by rat liver microsomes". Xenobiotica. 25 ( ... Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems.[3][2] Use by those with ... significant kidney problems or liver problems or who are pregnant is not recommended.[2][3] Gliclazide is in the sulfonylurea ...
"Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome ... In rabbits, liver cells sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to ... and increased liver enzymes in the blood due to liver damage.[4][54] Over 5 years of treatment statins result in 75 cases of ... Cholesterol synthesis appears to occur mostly at night,[112] so statins with short half-lives are usually taken at night to ...
Comparison of human liver and kidney microsomes and mammalian enzymes". Biochemical Pharmacology. 60 (1): 7-17. doi:10.1016/ ... While the adult liver is dominated by the expression of FMO3 and FMO5, the fetal liver is dominated by the expression of FMO1 ... FMO3 is highly concentrated in the liver, but is also expressed in the lungs. FMO4 is expressed mostly in the liver and kidneys ... FMO2 is the most abundant of the FMO's and is mostly expressed in the lungs and kidneys, with lower expression in the liver and ...
... of caffeine to theobromine and theophylline is catalyzed primarily by flavin-containing monooxygenase in liver microsomes". ... FMO3 is the most abundantly expressed FMO in the adult human liver [12]. Its structure and function and the implications of its ... 1995). "Flavin-containing monooxygenase mediated metabolism of psychoactive drugs by human brain microsomes". Brain Res. 672 (1 ... H2O FMO3 is the main flavin-containing monooxygenase isoenzyme that is expressed in the liver of adult humans. The human FMO3 ...
Rawal S, Coulombe RA (August 2011). "Metabolism of aflatoxin B1 in turkey liver microsomes: the relative roles of cytochromes ... Zhang JW, Liu Y, Cheng J, Li W, Ma H, Liu HT, Sun J, Wang LM, He YQ, Wang Y, Wang ZT, Yang L (2007). "Inhibition of human liver ... reducing the Fe-O2 adduct to give a short-lived peroxo state. ... principally in the liver. The Human Genome Project has ...
Rawal S, Coulombe RA (August 2011). "Metabolism of aflatoxin B1 in turkey liver microsomes: the relative roles of cytochromes ... liver damage, and liver cancer. An association between childhood stunting and aflatoxin exposure[5] has been reported in some ... resulting later in cirrhosis or carcinoma of the liver. Acute liver failure is made manifest by bleeding, edema, alteration in ... Aflatoxin Q1 (AFQ1), major metabolite of AFB1 in in vitro liver preparations of other higher vertebrates[18] ...
"Purification and properties of a 3 β-hydroxy-delta 5-C27-steroid oxidoreductase from rabbit liver microsomes". J. Biol. Chem. ...
Segal, H.L. and Brenner, B.M. (1960). "5′-Nucleotidase of rat liver microsomes". J. Biol. Chem. 235: 471-474. PMID 14444527. ...
P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes". Drug ...
3. Enzymic hydroxylation by rat-liver microsomes". Biochem. J. 66: 73-78. PMID 13426111. ... "Aminopyrine metabolism by multiple forms of cytochrome P-450 from rat liver microsomes: simultaneous quantitation of four ... "Immunochemical evidence for six forms of rat liver cytochrome P450 obtained using antibodies against purified rat liver ... Lang, M.A., Gielen, J.E. and Nebert, D.W. (1981). "Genetic evidence for many unique liver microsomal P-450-mediated ...
... determinants of inter-individual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. „ ...
marec 1997). "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and ... and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver". Drug ...
"Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults" (pdf). Departement de ...
"Amlodipine Metabolism in Human Liver Microsomes and Roles of CYP3A4/5 in the Dihydropyridine Dehydrogenation". Drug Metabolism ...
In tests with liver microsomes, dealkylation seemed to be mediated by CYP3A4, but other CYP enzymes appear to be involved as ... There are no relevant interactions related to cytochrome P450 (CYP) liver enzymes, although one inactivation pathway of ... Safinamide is contraindicated in people with severe liver impairment, with albinism, retinitis pigmentosa, severe diabetic ...
Mahfouz M (1981). "Effect of dietary trans fatty acids on the delta 5, delta 6 and delta 9 desaturases of rat liver microsomes ... Liver dysfunction: Trans fats are metabolized differently by the liver than other fats and interfere with delta 6 desaturase. ... "Province restricts trans fat in B.C." (Press release). British Columbia Ministry of Healthy Living and Sport. 7 March 2009. ... "B.C. tackles trans fat in food service establishments" (Press release). British Columbia Ministry of Healthy Living and Sport. ...
Bun SS, Ciccolini J, Bun H, Aubert C, Catalin J. Drug interactions of paclitaxel metabolism in human liver microsomes. J ...
... in human liver microsomes". Xenobiotica. 35 (3): 227-37. doi:10.1080/00498250400028239. PMID 16019948.. ...
... activity on arachidonic and linoleic acids studied with human recombinant enzymes and with human and rat liver microsomes". The ... liver, and ovary. However, 12-Hydroxyheptadecatrienoic acid (i.e. 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid or 12-HHT), a ... Liver International. 34 (9): 1428-44. doi:10.1111/liv.12541. PMC 4169337 . PMID 24661807. Bortuzzo, C; Hanif, R; Kashfi, K; ... Gastrointestinal and Liver Physiology. 294 (4): G948-62. doi:10.1152/ajpgi.00274.2007. PMID 18258795. Krieg, P; Kinzig, A; ...
The enzyme-catalyzed formation of bilirubin diglucuronide by a solublized preparation from cat liver microsomes". Biochim. ... Bock, K.W., Josting, D., Lilienblum, W. and Pfeil, H. (1979). „Purification of rat-liver microsomal UDP-glucuronyltransferase. ...
... and 3A4 in human liver microsomes". 》Archives of Biochemistry and Biophysics》 346 (1): 161-9. doi:10.1006/abbi.1997.0302. PMID ...
... by human liver microsomes and recombinant cytochrome P450 enzymes". Biochemical Pharmacology. 71 (9): 1377. doi:10.1016/j.bcp. ...
"Formation of 6β-hydroxy and 6-keto derivatives of estradiol-16-C14 by mouse liver microsomes". J. Am. Chem. Soc. 79: 1004-1005. ...
Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochemical Pharmacology. 24 (17): ...
Omura, T.; Sato, R. (1962). "A new cytochrome in liver microsomes". The Journal of Biological Chemistry. 237: 1375-1376. PMID ...
Schmoldt, A.; Benthe, H. F.; Haberland, G. (1 September 1975). "Digitoxin metabolism by rat liver microsomes". Biochemical ... Despite producing six living children, their marriage was reputedly unhappy. Soon after the move to the leased farm, her ... She and her sister later moved to Bloomsbury, London, in 1803 to live with their brother, Henry Milton, who was employed in the ... Garrow married her son, Thomas Adolphus, and the three lived together until Trollope's death in 1863. She was buried near four ...
Schmoldt, A.; Benthe, H. F.; Haberland, G. (1975-09-01). "Digitoxin metabolism by rat liver microsomes". Biochemical ... In her book Living in Denial: Climate Change, Emotions, and Everyday Life, Kari Norgaard's study of Bygdaby-a fictional name ... Norgaard, Kari Marie (2011), Living in Denial: Climate Change, Emotions, and Everyday Life, The MIT Press, doi:10.7551/mitpress ... Norgaard, K. M. (2011). Living in Denial: Climate Change, Emotions, and Everyday Life. MIT Press. ISBN 9780262015448. Dryzek, ...
Segal HL, Brenner BM (February 1960). "5'-Nucleotidase of rat liver microsomes". The Journal of Biological Chemistry. 235: 471- ... Elevated levels may indicate cholestasis, destruction of liver cells, hepatitis (liver inflammation), liver ischemia, a liver ... In other words, the test is used to determine if elevated protein levels are due to skeletal damage or liver damage. Normal ... The concentration of 5'nucleotidase protein in the blood is often used as a liver function test in individuals that show signs ...
Schmoldt, A; Benthe, HF; Haberland, G (1 September 1975). "Digitoxin metabolism by rat liver microsomes". Biochemical ...
THC is highly lipophilic and initially taken up by tissues that are highly perfused, such as the lung, heart, brain, and liver. ... "Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes". Life ... Metabolism occurs mainly in the liver by cytochrome P450 enzymes CYP2C9, CYP2C19, CYP2D6, and CYP3A4.[28][29] More than 55% of ...
Recent orders of birds and most mammals make ascorbic acid in their liver.[115] A number of species of passerine birds also do ... and the metabolism of microsome.[19] During biosynthesis, ascorbate acts as a reducing agent, donating electrons and preventing ... In 1957, J.J. Burns showed that some mammals are susceptible to scurvy as their liver does not produce the enzyme l- ... Native people living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in ...
... in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS ... liver) into methylcatechol and pyrrolidine, which in turn are glucuronated (uridine 5'-diphospho-glucuronosyl-transferase) ...
2004-02-01). «Metabolism of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops (humulus Lupulus), by Human Liver Microsomes» ... When Was Beer Invented?» Live Science Noiz kontsultatua: 2018-04-03. *↑ a b (Ingelesez) «Fermented beverage and food storage in ...
P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug ...
... in the liver to active metabolites.[32][33] The main active metabolite is 4-hydroxycyclophosphamide, which exists in ... "Enzymatic basis of cyclophosphamide activation by hepatic microsomes of the rat". The Journal of Pharmacology and Experimental ... liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects of phosphoramide ...
... for both 13-HODE and 9-HODE in human liver microsomes.[13][14][15] ... Gastrointestinal and Liver Physiology. 307 (6): G664-71. doi:10.1152/ajpgi.00064.2014. PMID 25035111.. ... "Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic ...
An infection can only begin after living salmonellae (not merely Salmonella-produced toxins) reach the gastrointestinal tract. ... "Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test". Mutation Research. ... liver, spleen, kidneys) to form secondary foci (septic form). Endotoxins first act on the vascular and nervous apparatus, ...
Schmoldt, A; Benthe, HF; Haberland, G (১ সেপ্টেম্বর ১৯৭৫)। "Digitoxin metabolism by rat liver microsomes."। Biochemical ... Gurney, E., Myers, F.W.H. and Podmore, F. (1886). Phantasms of the Living, Vols. I and II. London: Trubner and Co.. ...
Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate». Curr. Biol., 16, 3, ... Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate ... The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver». Biochem. J., 103, 2 ... The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver». Biochem. J., 115, 4, 1969, ...
... limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes.. Drug Metab. Dispos. 30 ... Cloning and sequence determination of a complementary DNA related to human liver microsomal cytochrome P-450 S-mephenytoin 4- ...
Plus 3-5 microsomes.. Alfalfa. Medicago sativa. 32[21]. Cultivated alfalfa is tetraploid, with 2n=4x=32. Wild relatives have 2n ... Hyraxes are considered to be the closest living relative to the Elephant.[20]. ...
To some of the participants, "microsomes" mean the ribonucleoprotein particles of the microsome fraction contaminated by other ... The ribosome (/ˈraɪbəˌsoʊm, -boʊ-/[1]) is a complex molecular machine, found within all living cells, that serves as the site ... O'Brien, T.W. (1971). "The General Occurrence of 55S Ribosomes in Mammalian Liver Mitochondria". J. Biol. Chem. 245: 3409.. ... During 1977, Czernilofsky published research that used affinity labeling to identify tRNA-binding sites on rat liver ribosomes ...
"Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate". Curr. Biol. 16 (3): ... "Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol ... "The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver". Biochem. J. 103 (2 ... "The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver". Biochem. J. 115 (4): 609- ...
... in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS ... MDPV undergoes CYP450 2D6, 2C19, 1A2,[17] and COMT phase 1 metabolism (liver) into methylcatechol and pyrrolidine, which in ...
Kuehl GE, Murphy SE: N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP- ... Kuehl GE, Murphy SE: N-glucuronidation of trans-3'-hydroxycotinine by human liver microsomes, Chem. Res. Toxicol., vol. 16, 12 ...
... living cells.[1] Microsomes can be concentrated and separated from other cellular debris by differential centrifugation. ... To get microsomes containing a specific CYP or for high amounts of active enzyme, microsomes are prepared from Sf9 insect cells ... In this way, cytochrome P450 in microsomes is concentrated and isolated. Microsomes have a reddish-brown color, due to the ... Researchers often select microsome lots based on the enzyme activity level of specific CYPs. Some lots are available to study ...
... in human liver microsomes. After incubation of the four constituents of ,i,Coptis chinensis,/i, in HLMs, the metabolism of the ... Human Liver Microsomes. HLMs used in this study were provided by the Research Institute for Liver Diseases Co. Ltd. (Shanghai, ... The microsomes were prepared from ten Mongolian individual human donor livers.. 2.4. Incubation Procedure [13, 14]. A typical ... However, metabolic interaction of the herbal constituents of Rhizoma Coptidis alkaloid in human liver microsomes has not been ...
... microsomes & other liver subcellular fractionsLarge pooled lots for reproducible, long-term studiesFractions carefully isolated ... Table 1. Relevant applications for liver subcellular fractions.. Metabolic Enzymes. Liver Microsomes. Liver S9 Fractions. Liver ... Table 3. Kinetic parameters for the Gibco 50 donor human liver microsome pool.. Isoform. Metabolite. Km(μM). Vmax (nmol/min/mg) ... 11 specialty human liver microsome pools. Prepared with 5 to 20 donors each and pooled for your convenience according to age, ...
Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes.. Yamazaki H1, Inoue K, Hashimoto M, Shimada T. ... In liver microsomes of 16 human samples, nicotine C-oxidation activities were correlated with CYP2A6 contents at 10 microM ... Nicotine C-oxidation by recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes was investigated ... on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. CYP2D6 was found to have minor roles ...
Sprague Dawley rat liver microsomes (RLM), mouse liver microsomes (MLM), Dunkin Hartley guinea pig liver microsomes (PLM) and ... including human liver microsomes (HLM), Rhesus monkey liver microsomes (RMLM), Cynomolgus monkey liver microsomes (CMLM), ... and mouse liver microsomes, and human liver s9. Drug Metab Dispos. 40:2041-2053. 2012.PubMed/NCBI View Article : Google Scholar ... The metabolic transformations of xanthotoxin in the liver microsomes of the 7 species were analyzed in further detail. On the ...
Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes.. S ... Thus, lathosterol 5-dehydrogenase is equally active which indicates that homozygotes liver microsomes are viable. Accordingly, ... 7-dehydrocholesterol into cholesterol by liver microsomes from seven controls and four Smith-Lemli-Opitz homozygous subjects. ... that is catalyzed by lathosterol-5-dehydrogenase was equally rapid in controls and homozygotes liver microsomes (120 +/- 8 vs ...
... microsomes & other liver subcellular fractionsLarge pooled lots for reproducible, long-term studiesFractions carefully isolated ... Table 1 - Relevant applications for liver subcellular fractions Metabolic Enzymes Liver Microsomes Liver S9 Fractions Liver ... Table 3 - Kinetic parameters for the GIBCO® 50 donor human liver microsome pool Isoform Metabolite Km(μM) Vmax (nmol/min/mg) ... Human microsome pools and subcellular fractions Subcellular fractions, derived from the endoplasmic reticulum of liver, contain ...
Phenacetin O-deethylase (POD) activities in human liver microsomes at substrate concentrations of 10 and 500 microM were ... in phenacetin O-deethylation were investigated using human liver microsomes and recombinant proteins. ... Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes Xenobiotica. 1999 Sep;29(9): ... 3. In the absence of alpha-naphthoflavone, the POD activity in pooled human liver microsomes at 500 microM phenacetin was ...
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... purified from pig liver microsomes. The stoichiometric relationship between NADPH and substrate during the course of … ... dependent monooxygenase of pig liver microsomes Biochem Pharmacol. 1982 Mar 1;31(5):745-52. doi: 10.1016/0006-2952(82)90458-0. ... purified from pig liver microsomes. The stoichiometric relationship between NADPH and substrate during the course of the ...
Although the activity of propofol glucuronidation in liver is higher, glucuronidation in kidney may be a substantial ... The high degree of hydroxylation activity in liver microsomes is consistent with the blood flow-limited hepatic clearance of ... Prediction of total propofol clearance based on enzyme activities in microsomes from human kidney and liver Eur J Clin ... Conclusion: The high degree of hydroxylation activity in liver microsomes is consistent with the blood flow-limited hepatic ...
Metabolism of 4′-(9-Acridinylamino)methanesulfon-m-anisidide by Rat Liver Microsomes. D. D. Shoemaker, R. L. Cysyk, P. E. ... Metabolism of 4′-(9-Acridinylamino)methanesulfon-m-anisidide by Rat Liver Microsomes ... Metabolism of 4′-(9-Acridinylamino)methanesulfon-m-anisidide by Rat Liver Microsomes ... Metabolism of 4′-(9-Acridinylamino)methanesulfon-m-anisidide by Rat Liver Microsomes ...
Protein Binding of Bile Acids in Rat Liver Cytosol and Microsomes Julia Ellis; Julia Ellis ... Julia Ellis, Barbara H. Moreland, G. M. Murphy; Protein Binding of Bile Acids in Rat Liver Cytosol and Microsomes. Clin Sci ( ...
Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal ... of the imidazobenzodiazepine midazolam to its alpha-hydroxy and 4-hydroxy metabolites was studied in vitro using human liver ...
CYP2C19 Participates in Tolbutamide Hydroxylation by Human Liver Microsomes. Michael R. Wester, Jerome M. Lasker, Eric F. ... CYP2C19 Participates in Tolbutamide Hydroxylation by Human Liver Microsomes. Michael R. Wester, Jerome M. Lasker, Eric F. ... CYP2C19 Participates in Tolbutamide Hydroxylation by Human Liver Microsomes. Michael R. Wester, Jerome M. Lasker, Eric F. ... CYP2C19 Participates in Tolbutamide Hydroxylation by Human Liver Microsomes Message Subject (Your Name) has forwarded a page to ...
Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4. Drug Metab Dispos. 1996;24(9): ... Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass ... Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N-oxide. Chem Res Toxicol. 1992; ... Metabolism and bioactivation of clozapine by human liver in vitro. J Pharmacol Exp Ther. 1995;272(3):984-90.PubMedGoogle ...
Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine ... Human liver microsomal CYP2B6 activities were investigated using bupropion hydroxylation as probe substrate marker. The results ... In conclusion, the results from this study demonstrated that MAO inhibitors can inactivate human liver microsomal CYP2B6. The ... study was to evaluate the metabolism dependent inhibition of CYP2B6 catalyzed bupropion hydroxylation in human liver microsomes ...
A total of twelve phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes a total of nineteen ... A total of 12 phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes 19 metabolites, ... This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ... This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ...
Identification of di-(2-ethylhexyl) phthalate-induced carboxylesterase 1 in C57BL/6 mouse liver microsomes: purification, cDNA ... and it was found to contribute significantly to temocapril hydrolase activity in mouse liver microsomes. To identify the ...
CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes ... in human liver microsomes.. *Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump ... In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in ... These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. In conclusion, our data ...
Assay with Human Liver Microsomes.. The basic incubation medium contained 0.1 mg/ml human liver microsomes, 0.5 mM NADP+, 2.0 ... Preparation of Human Liver Microsomes.. Six histologically normal liver samples were obtained from Japanese patients with ... and dog liver microsomes, and 3-hydroxyquinine is the main metabolite of quinine in these animal livers (Zhao and Ishizaki, in ... aroundKm value in human liver microsomes) of quinine was incubated with microsomes equivalent to 0.1 mg of protein/ml. A linear ...
Characterization of CYP2A6 involved in 3-hydroxylation of cotinine in human liver microsomes.. M Nakajima, T Yamamoto, K ... Characterization of CYP2A6 involved in 3-hydroxylation of cotinine in human liver microsomes.. M Nakajima, T Yamamoto, K ... Characterization of CYP2A6 involved in 3-hydroxylation of cotinine in human liver microsomes.. M Nakajima, T Yamamoto, K ... The Km value of the expressed CYP2A6 (264.7 microM) was almost identical to that of human liver microsomes. In conclusion, ...
The metabolism of n-hexane by rat skeletal muscle, liver, lung and brain microsomes SARAH J. CROSBIE; SARAH J. CROSBIE ... SARAH J. CROSBIE, FAITH M. WILLIAMS, PETER G. BLAIN; The metabolism of n-hexane by rat skeletal muscle, liver, lung and brain ... microsomes. Biochem Soc Trans 1 May 1994; 22 (2): 130S. doi: https://doi.org/10.1042/bst022130s ...
Human liver microsomes.. Human liver samples (n = 14) were obtained, as excess material removed during surgery on the liver, ... Assay with human liver microsomes.. The basic incubation medium contained 0.1 or 0.2 mg/ml microsomes, 0.5 mM NADP+, 2.0 mM ... in human liver microsomes.. The immunoinhibition of CIT N-demethylation was examined by preincubating human liver microsomal ... Kinetic profile of CIT N-demethylation in human liver microsomes.. Eadie-Hofstee plots for the N-demethylation of CIT (2.5-500 ...
BioAssay record AID 31223 submitted by ChEMBL: Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT) activity in rat liver microsome.
Incorporation of 14C into the phospholipid components of the liver microsomes isolated by a conventional method was determined ... Leyck S., Freundt K.J. (1978) Response of Phospholipid Metabolism to Thiram in Rat Liver Microsomes. In: Deutsche ... strongly with an inhibition of MFO as shown by a decrease in the O-demethylation of p-nitroanisol in prepared liver microsomes ... After 16 h the livers were subjected to extracorporeal perfusion for 1 h, the perfusate containing ca. 10 μCi u 14C glucose/100 ...
In the present investigation it was found that benzene was metabolized at a rate 20-65-fold higher in liver microsomes from ... The data indicate that benzene is metabolized mainly by the ethanol-inducible P-450 form in liver microsomes and that the ... Benzene Metabolism by Ethanol-, Acetone-, and Benzene-inducible Cytochrome P-450 (IIE1) in Rat and Rabbit Liver Microsomes. ... Benzene Metabolism by Ethanol-, Acetone-, and Benzene-inducible Cytochrome P-450 (IIE1) in Rat and Rabbit Liver Microsomes ...
Metabolic stability in human liver microsomes assessed as compound remaining at 1 uM after 60 mins by HPLC-MS analysis. ...
Involvement of cytochrome P-450c in alpha-naphthoflavone metabolism by rat liver microsomes.. M J Andries, G W Lucier, J ... Involvement of cytochrome P-450c in alpha-naphthoflavone metabolism by rat liver microsomes.. M J Andries, G W Lucier, J ... Involvement of cytochrome P-450c in alpha-naphthoflavone metabolism by rat liver microsomes.. M J Andries, G W Lucier, J ... Neither anti-P-450c nor anti-P-450d inhibited ANF metabolism in uninduced rat liver microsomes. In a reconstituted enzyme ...
... Araya, Z Uppsala ... Fourteen recombinant expressed cytochrome P450 (CYP) enzymes, human liver microsomes from different donors, and selective ... bile acid; 6 alpha-hydroxylation; CYP3A4; human liver; BILE-ACIDS; PIG-LIVER; METABOLISM; URINE; CYTOCHROME-P-450; ... The aim of the present study was to identify the enzymes in human liver catalyzing hydroxylations of bile acids. ...
... ... METHODS: Using pooled human liver microsomes, the in vitro inhibitory effects of isoniazid on CYP1A2 (phenacetin O-deethylation ... CYP2C19 and CYP3A4 in human liver microsomes. Co-administration of isoniazid and drugs that are primarily metabolised by these ...
  • The present study aimed to identify the similarities and differences in xanthotoxin metabolism in liver microsomes of 7 mammalian species, including human liver microsomes (HLM), Rhesus monkey liver microsomes (RMLM), Cynomolgus monkey liver microsomes (CMLM), Sprague Dawley rat liver microsomes (RLM), mouse liver microsomes (MLM), Dunkin Hartley guinea pig liver microsomes (PLM) and Beagle dog liver microsomes (DLM). (spandidos-publications.com)
  • Mays DC, Hilliard JB, Wong DD, Chambers MA, Park SS, Gelboin HV and Gerber N: Bioactivation of 8-methoxypsoralen and irreversible inactivation of cytochrome P-450 in mouse liver microsomes: Modification by monoclonal antibodies, inhibition of drug metabolism and distribution of covalent adducts. (spandidos-publications.com)
  • Identification of di-(2-ethylhexyl) phthalate-induced carboxylesterase 1 in C57BL/6 mouse liver microsomes: purification, cDNA cloning, and baculovirus-mediated expression. (sigmaaldrich.com)
  • The purified enzyme possessed temocapril hydrolase activity, and it was found to contribute significantly to temocapril hydrolase activity in mouse liver microsomes. (sigmaaldrich.com)
  • Immunoblot analysis of mouse liver microsomes with an antibody raised against a rat CYP2D enzyme indicated that the mouse liver contained a P450 enzyme(s) immunochemically related to the rat CYP2D enzyme. (elsevier.com)
  • The antibody inhibited propranolol ring-hydroxylase and imipramine 2-hydroxylase activities, as well as testosterone 16α-hydroxylase activity, a typical reaction of mouse CYP2D9, but not debrisoquine 4- hydroxylase activity in mouse liver microsomes. (elsevier.com)
  • To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). (edu.au)
  • Genetic differences in metabolism of polycyclic aromatic carcinogens and aromatic amines by mouse liver microsomes. (elsevier.com)
  • The metabolites of jatrorrhizine [ 8 ] have been analyzed in liver microsomes of rat. (hindawi.com)
  • Biotransformation of the imidazobenzodiazepine midazolam to its alpha-hydroxy and 4-hydroxy metabolites was studied in vitro using human liver microsomal preparations. (nih.gov)
  • Our laboratory has previously reported clastogenic effects of metabolites of ANF, and in the present study we reexamined the role of P-450c in ANF metabolism by both uninduced and TCDD-induced rat liver microsomes, using monospecific polyclonal antibodies to P-450c and P-450d. (aspetjournals.org)
  • Using a cocktail probe of CYP450 isoform-specific substrates and their metabolites, we then carried out in vitro enzymatic studies in liver microsomal incubation systems via ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Finally, we verified our results at the messenger ribonucleic acid (mRNA) and protein level through quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical detection. (biomedcentral.com)
  • Multiple UDP-glucuronosyltransferases in human liver microsomes glucuronidate both R- and S-7-hydroxywarfarin into two metabolites. (uams.edu)
  • Two metabolites generated by the liver microsome system were detected and identified as hydroxylated cardamonin. (nature.com)
  • These results suggested that psoralen and isopsoralen are modest hepatotoxic agents, as their reactive metabolites could be deactivated by H 2 O and GSH in the liver, which partly contributes to the ingestion of psoralen-containing fruits and vegetables being safe. (mdpi.com)
  • After incubation with microsomes, the hydrocarbon substrate and produced metabolites were extracted then separated and quantified by radio-HPLC. (europa.eu)
  • On average, the hydroxylation rates of heptadecane incubated with male rat liver microsomes at the highest concentration tested (60 µM) varied from 78 ± 32 moles/hr/mg proteins in Sprague Dawley rats to 101 ± 20 pmoles/hr/mg proteins (total amount of metabolites formed) in Fischer 344 rats. (europa.eu)
  • Isolation and identification of new rapamycin dihydrodiol metabolites from dexamethasone-induced rat liver microsomes. (uclouvain.be)
  • 1. Rapamycin is metabolically transformed in rat liver microsomes to 3,4- and 5,6-dihydrodiol metabolites under the influence of the cytochrome P-450 mixed function oxygenase system. (uclouvain.be)
  • These metabolites were produced from dexamethasone-induced as well as from non-induced rat liver microsomes. (uclouvain.be)
  • Incubation of human liver microsomes with GSK5182 in the presence of NADPH resulted in the formation of three metabolites, M1, M2 and M3. (elsevier.com)
  • In addition, the specific cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) isoforms responsible for GSK5182 oxidation to the three metabolites were identified using a combination of correlation analysis, chemical inhibition in human liver microsomes and metabolism by expressed recombinant P450 and FMO isoforms. (elsevier.com)
  • In order to clarify the metabolism pathways of scandoside methyl ester , the analysis of metabolites profiling in four kinds of liver microsomes was performed by using an ultra-performance liquid chromatography / electrospray- tandem mass spectrometry (UPLC-ESI-MS). The data obtained from the 0 h-incubation and the 2 h-incubation were compared and analyzed. (bvsalud.org)
  • After incubation, 5 metabolites of scandoside methyl ester were found in rat , Beagles, rhesus monkey and human liver microsome . (bvsalud.org)
  • Incubation with pooled human liver microsomes yielded 15 metabolites of EG-018 belonging to six different metabolite subgroups, and 21 metabolites of EG-2201 belonging to seven different metabolite subgroups, respectively. (dshs-koeln.de)
  • In Smith-Lemli-Opitz homozygotes, the transformation of 7-dehydrocholesterol to cholesterol by hepatic microsomes was blocked although 7-dehydrocholesterol was produced abundantly from lathosterol. (jci.org)
  • Hepatic hydroxylation and glucuronidation activities were also performed separately using human liver microsomes. (nih.gov)
  • Although glucuronidation activity in microsomes from kidneys was comparable to that from liver, the hepatic intrinsic clearance predicted from in vitro study was higher than that in kidneys due to the larger tissue volume and higher protein concentration. (nih.gov)
  • The high degree of hydroxylation activity in liver microsomes is consistent with the blood flow-limited hepatic clearance of propofol. (nih.gov)
  • 4′-(9-Acridinylamino)methanesulfon- m -anisidide (m-AMSA) is metabolized by a hepatic microsomal enzyme system composed of rat liver microsomes, a reduced nicotinamide adenine dinucleotide phosphate-generating system, cytosolic protein (or glutathione), and oxygen. (aacrjournals.org)
  • Western blotting revealed that the absorbed anti-human CYP2C9 preparation reacted with only recombinant CYP2C9 and the corresponding native protein in hepatic microsomes, and no longer recognized CYP2C19 and CYP2C8. (aspetjournals.org)
  • 15%) inhibitory effect on S -mephenytoin 4′-hydroxylation by purified CYP2C19 or hepatic microsomes containing CYP2C19. (aspetjournals.org)
  • Aggregates were formed when clear supernatants from hepatic microsomes that had been treated with steapsin were desalted and concentrated. (sciencemag.org)
  • No metabolism was detected when pristane or dodecylcyclohexane were incubated with human or rat hepatic microsomes (irrespective of the rat strain investigated). (europa.eu)
  • To verify the direct inhibitive effect of CO on CYP2E1 activity, rat hepatic microsomes were isolated by ultracentrifuge and incubated with ruthenium-containing CO releasing molecular (tricarbonyldichlororuthenium dimmer, CORM-2) which has been confirmed to possess the effects similar to CO administration as a gas. (thefreedictionary.com)
  • The consequences of induction by CBZ, carbamazepine-10,11-epoxide (CBZE), phenobarbital (PB) and clofibrate (CFB) on the metabolism of VPA and (E)-2-ene VPA by rat hepatic microsomes were examined. (ubc.ca)
  • Cytochrome P-450b constituted 65 % of the total hepatic cytochrome P-450 content in the PB induced microsomes and ranged from 31 to 66 % in the CBZ and CBZE groups over the 14 day treatment period. (ubc.ca)
  • A new isozyme of cytochrome P-450 has been purified to electrophoretic homogeneity from hepatic microsomes of rabbits treated chronically with ethanol. (elsevier.com)
  • Tegafur (FT) is a prodrug of 5-fluorouracil (5-FU) used in cancer chemotherapy, and the bioactivation of FT to 5-FU is mainly catalyzed by cytochrome P450 (CYP) in hepatic microsomes. (elsevier.com)
  • Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. (nih.gov)
  • Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. (sigmaaldrich.com)
  • The objective of the study was to evaluate the metabolism dependent inhibition of CYP2B6 catalyzed bupropion hydroxylation in human liver microsomes by monoamine oxidase (MAO) inhibitors and to predict the drug-drug interaction potential of monoamine oxidase inhibitors as perpetrators of drug interaction. (sigmaaldrich.com)
  • These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. (unboundmedicine.com)
  • The mutual inhibition between quinine and etoposide with their major metabolic pathways ( i.e. quinine 3-hydroxylation and etoposide 3′-demethylation) was examined in vitro by human liver microsomes. (aspetjournals.org)
  • More importantly, if a mutual inhibition between quinine and etoposide in human liver microsomes would occur, it should provide further evidence for the role of CYP3A4 involvement in the metabolism of both quinine and etoposide. (aspetjournals.org)
  • This effect correlated strongly with an inhibition of MFO as shown by a decrease in the O-demethylation of p-nitroanisol in prepared liver microsomes. (springer.com)
  • Propoxyphene and norpropoxyphene exhibited the greatest inhibition with CYP3A in human liver microsomes, followed by CYP3A4(+b5), and CYP3A5(+b5). (iupui.edu)
  • The KI values of propoxyphene and CYP3A4(+b5) and human liver microsomes fall within the range of reported therapeutic blood levels of propoxyphene, with reversible inhibition constants (Ki values) above therapeutic blood concentrations for propoxyphene and norpropoxyphene. (iupui.edu)
  • Inhibition studies using cytochrome P450 inhibitors such as quinidine, quinine, and α-naphthoflavone or polyclonal antibodies raised against rat P450-2D and -1A enzymes did not make clear which P450 enzymes are involved in bunitrolol 4-hydroxylation in rabbit liver microsomes. (elsevier.com)
  • [2] [3] Therefore, microsomes are a valuable tool for investigating the metabolism of compounds (enzyme inhibition, clearance and metabolite identification) and for examining drug-drug interactions by in vitro -research. (wikipedia.org)
  • Some lots are available to study specific populations (example: lung microsomes from smokers or non-smokers) or divided into classifications to meet target CYP activity levels for inhibition and metabolism studies. (wikipedia.org)
  • Three European mistletoe products (Helixor® A, Helixor® M and Helixor® P from mistletoe grown on firs, apple trees and pines, respectively) were tested for inhibition of nine major cytochrome P450 (CYP) isoenzymes in a test system using pooled human liver microsomes and for induction of five CYP isoforms in human hepatocytes cultivated in vitro according to the relevant guideline. (biomedcentral.com)
  • InVitroCYP is the first product for the ADME-Tox market that delivers microsome products specifically for metabolic or inhibition studies without compromising P450 values, and without the time and cost of custom blending. (thefreedictionary.com)
  • We investigated the contribution of the liver and kidneys to propofol metabolism in humans using an in vitro-in vivo scale up approach. (nih.gov)
  • Based on the background as discussed above, we conducted this study to assess the mutual interaction potential of quinine and etoposide in vitro, as well as to confirm further that etoposide and quinine are metabolized mainly via CYP3A in human liver microsomes. (aspetjournals.org)
  • METHODS: Using pooled human liver microsomes, the in vitro inhibitory effects of isoniazid on CYP1A2 (phenacetin O-deethylation), CYP2A6 (coumarin 7-hydroxylation), CYP2C9 (tolbutamide hydroxylation), CYP2CI9 (S-mephenytoin 4'-hydroxylation), CYP2D6 (dextromethorphan O-demethylation), CYP2E1 (chlorzoxazone 6-hydroxylation) and CYP3A4 (midazolam 1'-hydroxylation) activities were examined. (omicsonline.org)
  • This review summarizes these findings and discusses their implications for the use of human liver microsomes and hepatocytes for in vitro studies of drug metabolism and enzyme induction, which play a key role in drug development. (ovid.com)
  • Human liver microsomes contain a wide variety of drug metabolizing enzymes and are commonly used to support in vitro ADME (Absorption, Distribution, Metabolism and Excretion) studies. (xenotech.com)
  • In the present study, an in vitro metabolism study of cardamonin in human and animal liver microsomes was performed. (nature.com)
  • Microsomes are a valuable tool for investigating drug metabolism and examining in vitro drug-drug interactions. (sciencemag.org)
  • Metabolism of chloroquine in microsomes of mice liver tissue was studied in vitro by means of thin-layer and microcolumn liquid chromatographies. (msk.ru)
  • Human liver microsomes (20 mg/ml) were purchased from In Vitro Technologies, Inc. Baltimore, USA as pooled, mixed gender human liver microsomes, art. (biomedcentral.com)
  • This study examines the in vitro metabolism of EG-018 and its 5F-analogue EG-2201 by means of comparing three different in vitro models: pooled human liver microsomes, cytochrome P450 isoenzymes, and a fungal approach utilizing the filamentous fungus Cunninghamella elegans LENDNER, which is known for its ability to mimic human biotransformation of xenobiotics. (dshs-koeln.de)
  • Involvement of cytochrome P-450c in alpha-naphthoflavone metabolism by rat liver microsomes. (aspetjournals.org)
  • Digitoxin metabolism by rat liver microsomes. (openrepository.com)
  • I. Presence of glycoproteins in microsomes and cytosol. (rupress.org)
  • The glycoproteins of microsomes and cytosol were studied. (rupress.org)
  • Researchers can select from pure microsomes or S9 fractions, or animal liver cytosol. (sciencemag.org)
  • Evidence was presented to indicate that the binding of benzo(a)pyrene (50328) (BaP) to a protein in rat liver cytosol facilitates its oxidation by microsomal enzymes. (cdc.gov)
  • Sephadex G-100 gel permeation chromatography of rat liver cytosol saturated with carbon- 14 labeled BaP resulted in two peaks of protein bound radioactivity. (cdc.gov)
  • Also, cross-mixing experiments indicate that the cytosol(105,000g supernatant) from senescent animals is inhibitory to protein synthesis with microsomes from 12 month old rats. (illinois.edu)
  • The combination of cytosol from 12 month old animals and microsomes from senescent animals functioned most often like the senescent system. (illinois.edu)
  • Metabolism of m-AMSA is more rapid with microsomes prepared from rats pretreated with phenobarbital or 3-methylcholanthrene. (aacrjournals.org)
  • In the present investigation it was found that benzene was metabolized at a rate 20-65-fold higher in liver microsomes from ethanol- or acetone-treated rats than in microsomes from control animals. (aacrjournals.org)
  • One high affinity site [ K m = 19 ± 5 (SD) µ m ] and one low affinity site [K m = 0.3 ± 0.1 m m ] for benzene metabolism were present in microsomes of acetone-treated rats, and similar sites were seen in microsomes from control or ethanol-treated rats. (aacrjournals.org)
  • These rat liver microsomes are prepared from Sprague Dawley rats and are suitable as controls in Western applications. (oxfordbiomed.com)
  • Further studies of the induction of the liver microsomal drug-hydroxylating enzyme system by pretreatment of rats with various drugs are presented. (rupress.org)
  • Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats. (openrepository.com)
  • The metabolism of the environmental carcinogen fluoroanthene by human liver microsomes was compared to that by liver microsomes from rats treated with Aroclor 1254. (mysciencework.com)
  • Liver microsomes from Aroclor 1254-treated rats produced the R,R enantiomer of the diol in 75-78% enantiomeric excess, while human liver microsomes produced this enantiomer in only 6-12% excess. (mysciencework.com)
  • These CYPs are highly abundant in livers of rats, mice and humans, but present in all other organs and organisms as well. (wikipedia.org)
  • Oxidation of protein bound BaP, GST rich fractions, by microsomes from control or 3- methylcholanthrene treated rats was significantly enhanced as compared to ethanol suspended BP. (cdc.gov)
  • Protein synthesis as indicated by the incorporation of 14 C-leucine or a mixture of 14 C-labelled amino acids into cold TCA-insoluble material by liver microsomal fractions of mature adult (12 months) and old (20-31 months) female rats was investigated. (illinois.edu)
  • We provide liver subcellular fractions from a variety of tox species, including human, nonhuman primates (Cynomolgus Monkey and Rhesus Monkey), dog (Beagle), rat (Sprague-Dawley), mouse (CD-1), and trout (Oncorhynchus mykiss). (thermofisher.com)
  • Relevant applications for liver subcellular fractions. (thermofisher.com)
  • J. 314 , 1-14] was investigated by measuring the latency of diacylglycerol acyltransferase (DGAT) in microsomal fractions obtained from rat liver homogenates. (biochemj.org)
  • They are produced by mechanically homogenizing cells to fragment the endoplasmic reticulum, the fractions of which reform into microsomes and are collected via differential centrifugation. (sciencemag.org)
  • Our broad selection of liver and intestinal tissue fractions are highly characterized for important metabolizing enzymes such as CYPs, UGTs, and other enzymes. (corning.com)
  • The activation of POD activity in human liver microsomes by alphanaphthoflavone was inhibited by 100 microM aniline, anti-CYP2E1 antibody, 1 microM ketoconazole and anti-CYP3A4 antibody. (nih.gov)
  • 4. Inter-individual differences in the effects of alpha-naphthoflavone on POD activity in human liver microsomes were observed, and the involvement of CYP3A4 as well as CYP1A2 in POD activity in human liver was identified even at a low substrate concentration. (nih.gov)
  • These results suggest that CYP3A4 is the major isoenzyme and CYP2C19 is the minor form involved in the major metabolic pathway for CIT in human liver microsomes. (aspetjournals.org)
  • CONCLUSIONS: As the peak plasma concentrations of isoniazid are around 30-50 microM, isoniazid at clinically relevant concentrations reversibly inhibits CYP2C19 and CYP3A4 activities, and mechanistically inactivates CYP1A2, CYP2A6, CYP2C19 and CYP3A4 in human liver microsomes. (omicsonline.org)
  • Liver microsomal testosterone 6β-hydroxylase (CYP3A4) activity was slightly greater in females than males, but the difference was not significant. (ovid.com)
  • Furthermore, CYP3A4 induction in hepatocytes isolated from cirrhotic liver was comparable to that in normal hepatocytes, which supports the "healthy hepatocyte, sick environment" hypothesis of liver cirrhosis. (ovid.com)
  • Propoxyphene, norpropoxyphene, and proadifen were characterized in these studies with CYP3A4(+b5), CYP3A5(+b5) and pooled human liver microsomes. (iupui.edu)
  • Both compounds formed metabolic-inhibitor complexes with vi CYP3A4(+b5) and CYP3A5(+b5), but not with human liver microsomes. (iupui.edu)
  • Proadifen was a more potent inhibitor of CYP3A4(+b5) than of human liver microsomes and CYP3A5(+b5). (iupui.edu)
  • The KI values of norpropoxyphene and CYP3A4(+b5) and human liver microsomes are higher than most reported blood levels, except for blood levels after repeated dosing of propoxyphene at high concentrations. (iupui.edu)
  • The IC(50) of MAB-1A2 for the formation of the mono-hydroxylated products was 1 micromol/l, but neither other selective inhibitor nor substrate probes, including coumarin (CYP2D6), sulphaphenzole (CYP2C9/10), omeprazole (CYP2C19), quinidine (CYP2D6), diethyldithiocarbamate (CYP2E1), troleandomycin (CYP3A4) and keteconazole (CYP3A4), did so with human liver microsomes and concluded that Daidzein mono-hydroxylated products are principally metabolized by CYP1A2 in human. (blogspot.com)
  • Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes. (growkudos.com)
  • Although expression of CYP2C19 in human liver is less than that of CYP2C9, it may play an important role in tolbutamide disposition in subjects expressing either high levels of CYP2C19 or a catalytically deficient CYP2C9 enzyme. (aspetjournals.org)
  • Correlation analysis between the known P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole formation in samples from 14 human liver microsomes showed that albendazole hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation correlates with CYP2C19 and CYP2J2 activities. (unboundmedicine.com)
  • 001) between cotinine 3'-hydroxylase activities at low (50 microM) and high (1 microM) cotinine concentrations in 20 human liver microsomes suggested the contribution of a single enzyme to cotinine 3'-hydroxylation. (aspetjournals.org)
  • Studies to assess the enzyme kinetic behavior and to identify the cytochrome P450 (CYP) isoform(s) involved in the major metabolic pathway ( N -demethylation) for citalopram (CIT), a selective serotonin reuptake inhibitor, were performed using human liver microsomes and cDNA-expressed human cytochrome P450 isoforms. (aspetjournals.org)
  • These findings clearly suggest that CYP2A6 is a principal enzyme responsible for the bioactivation process of tegafur in human liver microsomes. (aacrjournals.org)
  • We have analyzed these data to examine whether the expression of CYP enzyme activity in liver microsomes and isolated hepatocytes or the inducibility of CYP enzymes in cultured hepatocytes is influenced by the gender, age, or ethnicity of the donor (the latter being limited to Caucasians, African Americans, and Hispanics due to a paucity of livers from Asian donors). (ovid.com)
  • We investigated the enzyme kinetics of buprenorphine and norbuprenorphine glucuronidation in human liver microsomes and UDP-glucuronosyltransferase (UGT) Supersomes. (eurekaselect.com)
  • Additionally, Sekisui XenoTech offers a patented Reaction Phenotyping Kit designed to identify the human liver CYP or UGT enzyme(s) responsible for xenobiotic metabolism. (xenotech.com)
  • Microsomes are typically used as the enzyme source for the measurement of metabolic stability and for reaction phenotyping because they express the major drug-metabolizing enzymes cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), along with others that contribute to drug metabolism. (edu.au)
  • We partially purified a P450 enzyme (designated P450 ML2d) from livers of male ddY mice by monitoring the cross-reactivity with the antibody. (elsevier.com)
  • These antibodies recognize and target its own enzyme produced in the liver. (mfine.co)
  • To get microsomes containing a specific CYP or for high amounts of active enzyme, microsomes are prepared from Sf9 insect cells or in yeast via heterologous expression. (wikipedia.org)
  • Researchers often select microsome lots based on the enzyme activity level of specific CYPs. (wikipedia.org)
  • This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled with a Q Exactive mass spectrometer. (frontiersin.org)
  • Human liver microsomes and hepatocytes are alternatives. (frontiersin.org)
  • For example, liver microsomes lack the cell membranes to mimic the physiological environment in hepatocytes. (frontiersin.org)
  • We have measured cytochrome P 450 (CYP) activity in nearly 150 samples of human liver microsomes and 64 samples of cryopreserved human hepatocytes, and we have performed induction studies in over 90 preparations of cultured human hepatocytes. (ovid.com)
  • Christa Kneip, Rolf Terlinden, Horst Beier and Genfu Chen, " Investigations Into the Drug-Drug Interaction Potential of Tapentadol in Human Liver Microsomes and Fresh Human Hepatocytes", Drug Metabolism Letters (2008) 2: 67. (eurekaselect.com)
  • Anti-IgG against ethanol-inducible cytochrome P-450 from rat (P-450j) or rabbit liver (P-450 LMeb) inhibited the microsomal benzene metabolism effectively in rat or rabbit liver microsomes, respectively, whereas preimmune IgG was without effect. (aacrjournals.org)
  • Unlike soluble cytochrome P-420, the cytochrome P-420 contained in the aggregates combines with drugs to give the characteristic difference spectra normally seen only with cytochrome P-450 contained in intact microsomes. (sciencemag.org)
  • Isozyme 4 of rabbit liver microsomal cytochrome P-450 was shown earlier in this laboratory to contain multiple NH 2 -terminal residues, whereas isozymes 2, 3a, 3b, and 3c have single, unique NH 2 -terminal sequences. (elsevier.com)
  • Liver microsomes are the most widely used for drug metabolism studies as they are easy to handle and commercially available. (frontiersin.org)
  • Yan Chang and David E. Moody, " Glucuronidation of Buprenorphine and Norbuprenorphine by Human Liver Microsomes and UDP-Glucuronosyltransferases", Drug Metabolism Letters (2009) 3: 101. (eurekaselect.com)
  • Nicotine C-oxidation by recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes was investigated using a convenient high-performance liquid chromatographic method. (nih.gov)
  • 1. The roles of different human cytochrome P450s (CYP) in phenacetin O-deethylation were investigated using human liver microsomes and recombinant proteins. (nih.gov)
  • Polyclonal antibodies were raised to CYP2C9 purified from human liver, and were then back-adsorbed against recombinant CYP2C19 coupled to a solid-phase support. (aspetjournals.org)
  • In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in the formation of hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole, respectively. (unboundmedicine.com)
  • In HLM (pH 7.4) and in insect microsomes containing recombinant human FMO3 (pH 9.5, 0.05% TritonX-100), MeDDC sulfine was formed at a rate of 3.3±0.6 (n=11) and 11.3±0.5 (n=3) nmol/mg/min, respectively. (elsevier.com)
  • The biotransformation of three radiolabelled alkanes, namely 14 C-heptadecane (n-alkane, 17 carbon atoms), 3 H-pristane (branched-alkane, 19 carbon atoms) and 3 H-dodecylcyclohexane (cyclo-alkane, 18 carbon atoms) was investigated using liver microsomes from three rat strains (Wistar, Sprague-Dawley and Fischer 344) and from three different pools of human donors (at least 10 donors in each case). (europa.eu)
  • Cardamonin was incubated with both human and animal liver microsomal incubation systems containing P450 reaction factors. (nature.com)
  • The cardamonin hydroxylation metabolic capacities of human and various other animals were investigated using the liver microsomal incubation system. (nature.com)
  • Serial cardamonin dilutions were used to perform a kinetic study in human liver microsomes. (nature.com)
  • Our recent study has shown that CYP3A/Cyp3a also plays a dominant role in the formation of 3-hydroxyquinine from quinine in mouse, rat, and dog liver microsomes, and 3-hydroxyquinine is the main metabolite of quinine in these animal livers (Zhao and Ishizaki, in press). (aspetjournals.org)
  • Nicotine is primarily metabolized to cotinine, and cotinine is further metabolized to trans-3'-hydroxycotinine in human liver, which is a major metabolite of nicotine in humans. (aspetjournals.org)
  • An unknown toxic ANF metabolite was formed only with a reconstituted P-450c system and with 3-MC- or TCDD-induced microsomes. (aspetjournals.org)
  • Described in this unit are methods for microsome isolation, as well as for the determination of metabolic stability and metabolite formation (including kinetics). (edu.au)
  • Similar extraction ratio of buagafuran (about 50%) and metabolite profiles were found in rat and human liver microsomes. (frontiersin.org)
  • In addition, a specific substrate of CYP2A6 and anti-CYP2A6 antibody inhibited the formation of 5-FU by 90% in human liver microsomes. (aacrjournals.org)
  • Use in combination with Liver Cytosolic Antigen Type 1 (LC-1) Antibody, IgG ( 2010711 ) when evaluating for AIH-2. (aruplab.com)
  • Liver-Kidney Microsome IgG antibody (anti-LKM), as detected by indirect immunofluorescent antibody (IFA) techniques, may be observed in patients with autoimmune hepatitis type 2 (AIH-2), AIH-2 associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), viral hepatitis C or D, and some forms of drug-induced hepatitis. (aruplab.com)
  • Liver Kidney Microsome - 1 Antibody is a protein antibody produced by the immune system of the body. (mfine.co)
  • Liver Kidney Microsome - 1 Antibody is a test done to evaluate and ascertain the cause of auto-immune related hepatitis. (mfine.co)
  • The test is to gauge if there are any other liver disorders related to the LKM-antibody. (mfine.co)
  • Liver Kidney Microsome - 1 Antibody can detect any other causes of liver damage or injury to the liver. (mfine.co)
  • Why is Liver Kidney Microsome - 1 Antibody suggested? (mfine.co)
  • What are the parameters measured in Liver Kidney Microsome - 1 Antibody? (mfine.co)
  • There is no special preparation for Liver Kidney Microsome - 1 Antibody. (mfine.co)
  • Tests like Liver Kidney Microsome - 1 Antibody are important and mfine helps people to get information about them easily. (mfine.co)
  • In the presence of NADPH and under aerobic conditions, thioether-containing organo-phosphorus and carbamate pesticides were oxidized by the FAD-dependent monooxygenase (EC 1.14.13.8) purified from pig liver microsomes. (nih.gov)
  • This bioactivation process is thought to be mediated by CYP, because NADPH is required for the conversion of tegafur to 5-FU in liver microsomes (9) , and its conversion rate has been shown to be accelerated by the pretreatment of mice with phenobarbital (10) , a well-known inducer of CYP. (aacrjournals.org)
  • Rabbit liver microsomes catalyzed the highly stereoselective, NADPH- and time-dependent S -oxidation of S -benzyl- l -cysteine (SBC), S -allyl- l -cysteine (SAC), S -(1,2-dichlorovinyl)- l -cysteine (DCVC), and S -(1,2,2-trichlorovinyl)- l -cysteine (TCVC) to their respective sulfoxides. (aspetjournals.org)
  • and (−)-flubatine, respectively, were incubated with liver microsomes from mouse and human in the presence of NADPH (β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt). (mdpi.com)
  • 0.01) between quinine 3-hydroxylase and etoposide 3′-demethylase activities in six different human liver microsomes was observed. (aspetjournals.org)
  • 01) in 10 different human liver microsomes. (aspetjournals.org)
  • Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. (nih.gov)
  • In liver microsomes of 16 human samples, nicotine C-oxidation activities were correlated with CYP2A6 contents at 10 microM substrate concentration, whereas such correlation coefficients were decreased when the substrate concentration was increased to 500 microM. (nih.gov)
  • Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti-CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. (nih.gov)
  • These results support the view that CYP2A6 has major roles for nicotine C-oxidation at lower substrate concentration and both CYP2A6 and 2B6 play roles at higher substrate concentrations in human liver microsomes. (nih.gov)
  • Enzymatic activity of propofol oxidation in renal microsomes was negligible. (nih.gov)
  • P450 ML2d had the oxidation activities for the rat CYP2D-substrates, such as propranolol 4-hydroxylation and imipramine 2-hydroxylation, in higher rates than those of the microsomes, but did not exhibit debrisoquine 4-hydroxylase activity. (elsevier.com)
  • The results showed that scandoside methyl ester 's major metabolic pathway in the liver microsomes is hydrolysis , oxidation and reduction reactions, and there are certain kinds differences between species. (bvsalud.org)
  • Compared with those from Caucasians and African Americans, liver microsomes from Hispanics had about twice the average activity of CYP2A6, CYP2B6, and CYP2C8 and half the activity of CYP1A2, although this apparent ethnic difference may be a consequence of the relatively low number of Hispanic donors. (ovid.com)
  • The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. (ovid.com)
  • The introduction of the double bond in lathosterol at C-5[6] to form 7-dehydrocholesterol that is catalyzed by lathosterol-5-dehydrogenase was equally rapid in controls and homozygotes liver microsomes (120 +/- 8 vs 100 +/- 7 pmol/mg protein per min, P = NS). (jci.org)
  • Several problems regarding the protein acceptor of the oligosaccharide from GEA (glucosylated endogenous acceptor) were investigated in the present work using rat liver microsomal subfractions. (springer.com)
  • Maximal metabolic velocity (V max ) of CYP probe substrates was decreased by 2.5- to 30-fold in tumor microsomes, accompanied by a corresponding decrease in their protein and mRNA expression levels. (aacrjournals.org)
  • Because of the need for a multi-part protein-system, microsomes are necessary to analyze the metabolic activity of CYPs. (wikipedia.org)
  • A decreased amino acid incorporation into protein occurred in the cell-free system from senescent rat liver. (illinois.edu)
  • Buetow, DE & Gandhi, PS 1973, ' Decreased protein synthesis by microsomes isolated from senescent rat liver ', Experimental Gerontology , vol. 8, no. 5, pp. 243-249. (illinois.edu)
  • Human microsome pools are fully characterized (K m and V max ) according to GLP standards for major cytochrome P450 activities and select Phase II enzymes using FDA recommended substrates (Tables 2-3). (thermofisher.com)
  • Microsomes were incubated with ¹⁴C labeled 18 carbon EFA substrates. (tamu.edu)
  • However, K m values and turnover numbers of substrates in tumor microsomes were not changed. (aacrjournals.org)
  • Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. (uams.edu)
  • UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family of enzymes, responsible for the biotransformation of several endogenous and exogenous chemicals, including therapeutic drugs. (aalto.fi)
  • In conclusion, the results from this study demonstrated that MAO inhibitors can inactivate human liver microsomal CYP2B6. (sigmaaldrich.com)
  • Cytochrome P450 and Phase II enzymes tested in Gibco human microsome pools. (thermofisher.com)
  • Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. (omicsonline.org)
  • Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics. (semanticscholar.org)
  • To characterize the metabolism of cardamonin by the P450 enzymes in human and animal liver microsomes. (nature.com)
  • CYP 1A2 and 2E1 were identified as the P450 isozymes involved in the metabolism of cardamonin in human liver microsomes. (nature.com)
  • During this process, the numerous different phase I cytochrome P450 enzymes are concentrated within the microsomes. (sciencemag.org)
  • In this way, cytochrome P450 in microsomes is concentrated and isolated. (wikipedia.org)
  • 7 Tramadol is extensively metabolized in the liver by the cytochrome P450 monooxygenases followed by conjugation reactions producing inactive glucuronides and sulfates (for details, https://www.pharmgkb.org/pathway/PA165946349 ). (aappublications.org)
  • 258:5649-5659 (1983)] reported that ANF metabolism by 3-MC-induced rat liver microsomes was only partially inhibited by antibodies against P-450c. (aspetjournals.org)
  • These antibodies kill the proteins in liver cells which can cause type 2 autoimmune hepatitis. (mfine.co)
  • In the present study, we investigated the N -demethylation of CIT in human liver microsomes and cDNA-expressed human P450s, to identify the principal isoform of P450s involved in this major metabolic pathway of CIT. (aspetjournals.org)
  • The purpose of the present study was to identify the human CYP isoform(s) involved in the metabolic activation of tegafur using human liver microsomes and cDNA-expressed human CYPs. (aacrjournals.org)
  • Moreover, cDNA-expressed CYP2A6 showed the highest activity for the formation of 5-FU among 10 cDNA-expressed CYPs, with a K m value similar to that found for the high-affinity component in human liver microsomes. (aacrjournals.org)
  • Based on the evaluation using cDNA-expressed enzymes, CYP2A6 showed the highest activity for 5-FU formation from R-FT with the K m value similar to that of the high-affinity component in microsomes. (elsevier.com)
  • Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes. (aspetjournals.org)
  • Microsomes of B-lymphoblastoid cells expressing human CYP2A6 exhibited cotinine 3'-hydroxylase activity. (aspetjournals.org)
  • The Km value of the expressed CYP2A6 (264.7 microM) was almost identical to that of human liver microsomes. (aspetjournals.org)
  • The metabolic transformations of xanthotoxin in the liver microsomes of the 7 species were analyzed in further detail. (spandidos-publications.com)
  • On the whole, the results of the present study provide a deeper understanding of the metabolic patterns of xanthotoxin in liver microsomes of different species, which may prove to be advantageous regarding the metabolic mechanisms of action of xanthotoxin. (spandidos-publications.com)
  • Species difference in codeine uridine diphosphate-glucuronyltransferase activity of liver microsomes. (semanticscholar.org)
  • A comprehensive range of liver microsome products from over 12 species, including mouse, rabbit, monkey, and chicken is now available. (sciencemag.org)
  • In order to facilitate requirements recommended by REACH, bespoke microsome products from other species or strains can also be supplied. (sciencemag.org)
  • Women Health: Human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein. (blogspot.com)
  • In the obersvation of " Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein" by Peng WX, Wang LS, Li HD, Abd El-Aty AM, Chen GL, Zhou HH. (blogspot.com)
  • Phenacetin O-deethylase (POD) activities in human liver microsomes at substrate concentrations of 10 and 500 microM were inhibited by 0.1 and 1 microM alpha-naphthoflavone and activated by 10 and 100 microM alpha-naphthoflavone. (nih.gov)
  • Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes. (jci.org)
  • Although the activity of propofol glucuronidation in liver is higher, glucuronidation in kidney may be a substantial contributor. (nih.gov)
  • This mannosyl-transfer activity was highest in microsomes and marginal in mitochondria, plasma and nuclear membranes. (biochemj.org)
  • Permeabilization of microsomes with taurocholate resulted in the doubling of the activity, indicating that DGAT activities of approximately equal magnitude occur on either aspect of the microsomal membrane. (biochemj.org)
  • Solubilization of microsomes also inhibited TCVC activity, whereas SBC, SAC, and DCVC activities were not affected. (aspetjournals.org)
  • The 4-hydroxylase activity of (+)-bunitrolol was slightly higher than that of (-)-bunitrolol in separated incubations containing male rabbit liver microsomes and an enantiomer concentration of 10 μM. (elsevier.com)
  • Corrected values of V[] and K[] for LA substrate were not calculated due to interference from high endogenous LA ubstrate concentrations in the liver microsomes. (tamu.edu)
  • Formation of a beta-glucuronidase-resistant glucuronide conjugate of digitoxin by dog liver microsomes. (openrepository.com)
  • While the human liver microsomal system demonstrated rapid clearance by CYP enzymes, the hepatocyte incubations showed much slower clearance, possibly providing some insight into the long duration of carfentanil's effects. (springer.com)
  • Human liver microsomal CYP2B6 activities were investigated using bupropion hydroxylation as probe substrate marker. (sigmaaldrich.com)
  • Differential evaluation of autoimmune liver disease of unknown etiology, especially autoimmune hepatitis (AIH) of childhood onset. (aruplab.com)
  • This test is ordered when your doctor is investigating your liver disease and wants to distinguish between different causes of liver injury and is suspecting autoimmune hepatitis. (1mg.com)
  • Possible explanations include the presence of high endogenous fatty acid concentration (especially 18:2n-6) inherent in the dog liver microsome preparations providing high amounts of competitive non-radioactively labeled substrate, or methodological differences used in other studies. (tamu.edu)
  • The aim of the present study was to identify the enzymes in human liver catalyzing hydroxylations of bile acids. (diva-portal.org)
  • ANF metabolism was inhibited to different extents in TCDD-induced microsomes by different preparations of anti-P-450c. (aspetjournals.org)
  • The formation of 5-FU from tegafur in human liver microsomes showed biphase kinetics with K m and V max values for the high-affinity component of 0.43 ± 0.05 m m and 4.02 ± 1.70 nmol/mg/min (mean ± SD, n = 4), respectively. (aacrjournals.org)
  • K m values determined with FMO3 were comparable to K m values from rabbit liver microsomes. (aspetjournals.org)
  • We have examined the 4-hydroxylation of bunitrolol in rabbit and rat liver microsomes. (elsevier.com)
  • Furthermore, the rate of clearance (V max /K m ) was 20- to 200-fold for the low-K m system compared with the high-K m system, indicating that enzymes in the low-K m system play a major part in the rabbit liver microsomal bunitrolol metabolism. (elsevier.com)
  • The difference in the Michaelis constants in the low-K m system, where the Km value of (-)-bunitrolol is one-eighth that of (+)-bunitrolol, is thought to cause the change in the stereoselectivity in rabbit liver microsome-mediated bunitrolol 4-hydroxylation. (elsevier.com)