Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.

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.

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.

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.

OXADIAZOLES bearing an oxygen at the 5-position. They are mesoionic, with delocalized positive and negative charges.

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.

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.

Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.

A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.

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.

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 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).

Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.

A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.

Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2.

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.

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.

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 sulfotransferase that catalyzes the sulfation of a phenol in the presence of 3'-phosphoadenylylsulfate as sulfate donor to yield an aryl sulfate and adenosine 3',5'-bisphosphate. A number of aromatic compounds can act as acceptors; however, organic hydroxylamines are not substrates. Sulfate conjugation by this enzyme is a major pathway for the biotransformation of phenolic and catechol drugs as well as neurotransmitters. EC 2.8.2.1.

Colorless reduced precursors of porphyrins in which the pyrrole rings are linked by methylene (-CH2-) bridges.

A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).

Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.

The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.

A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.

Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.

A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.

A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.

A skin irritant that may cause dermatitis of both primary and allergic types. Contact sensitization with DNCB has been used as a measure of cellular immunity. DNCB is also used as a reagent for the detection and determination of pyridine compounds.

A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)

Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.

Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.

17 beta-Hydroxy-4-androsten-3-ones. Testosterone derivatives formed by the substitution of one or more hydroxyl groups in any position.

A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.

The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.

Halogenated hydrocarbons refer to organic compounds containing carbon and hydrogen atoms, where one or more hydrogen atoms are replaced by halogens such as fluorine, chlorine, bromine, or iodine.

Oxidoreductases, N-Demethylating are enzymes that catalyze the oxidation of N-methyl groups to carbonyl groups, typically found in xenobiotic metabolism, involving the removal of methyl groups from various substrates using molecular oxygen.

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.

A polychlorinated pesticide that is resistant to destruction by light and oxidation. Its unusual stability has resulted in difficulties in residue removal from water, soil, and foodstuffs. This substance may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP-85-002, 1985). (From Merck Index, 11th ed)

A chemical by-product that results from burning or incinerating chlorinated industrial chemicals and other hydrocarbons. This compound is considered an environmental toxin, and may pose reproductive, as well as, other health risks for animals and humans.

Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

Naphthalene derivatives carrying one or more hydroxyl (-OH) groups at any ring position. They are often used in dyes and pigments, as antioxidants for rubber, fats, and oils, as insecticides, in pharmaceuticals, and in numerous other applications.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

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.

A carcinogen that is often used in experimental cancer studies.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.

Databases devoted to knowledge about PHARMACEUTICAL PRODUCTS.

Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.

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 benzyl-indazole having analgesic, antipyretic, and anti-inflammatory effects. It is used to reduce post-surgical and post-traumatic pain and edema and to promote healing. It is also used topically in treatment of RHEUMATIC DISEASES and INFLAMMATION of the mouth and throat.

A cholinesterase inhibitor that is used as a systemic insecticide, an acaricide, and nematocide. (From Merck Index, 11th ed)

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)

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.

A highly poisonous organochlorine insecticide. The EPA has cancelled registrations of pesticides containing this compound with the exception of its use through subsurface ground insertion for termite control and the dipping of roots or tops of non-food plants. (From Merck Index, 11th ed)

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.

Simultaneous resistance to several structurally and functionally distinct drugs.

The science concerned with the detection, chemical composition, and biological action of toxic substances or poisons and the treatment and prevention of toxic manifestations.

An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.

Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.

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.

Pigment obtained by the oxidation of epinephrine.

Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.

3'-Phosphoadenosine-5'-phosphosulfate. Key intermediate in the formation by living cells of sulfate esters of phenols, alcohols, steroids, sulfated polysaccharides, and simple esters, such as choline sulfate. It is formed from sulfate ion and ATP in a two-step process. This compound also is an important step in the process of sulfur fixation in plants and microorganisms.

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.

An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.

A selective triazine herbicide. Inhalation hazard is low and there are no apparent skin manifestations or other toxicity in humans. Acutely poisoned sheep and cattle may show muscular spasms, fasciculations, stiff gait, increased respiratory rates, adrenal degeneration, and congestion of the lungs, liver, and kidneys. (From The Merck Index, 11th ed)

Exogenous agents, synthetic and naturally occurring, which are capable of disrupting the functions of the ENDOCRINE SYSTEM including the maintenance of HOMEOSTASIS and the regulation of developmental processes. Endocrine disruptors are compounds that can mimic HORMONES, or enhance or block the binding of hormones to their receptors, or otherwise lead to activating or inhibiting the endocrine signaling pathways and hormone metabolism.

A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.

FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.

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 polychlorinated compound used for controlling a variety of insects. It is practically water-insoluble, but readily adheres to clay particles and persists in soil and water for several years. Its mode of action involves repetitive nerve-discharges positively correlated to increase in temperature. This compound is extremely toxic to most fish. (From Comp Biochem Physiol (C) 1993 Jul;105(3):347-61)

A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage.

Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.

An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.

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.

Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.

Mixture of 2- and 3-tert-butyl-4-methoxyphenols that is used as an antioxidant in foods, cosmetics, and pharmaceuticals.

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.

The rate dynamics in chemical or physical systems.

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).

Aminopyrine N-Demethylase is an enzyme, specifically a cytochrome P450 isoform, involved in the metabolism of drugs and xenobiotics, responsible for catalyzing the N-demethylation reaction.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite.

Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.

Six-carbon alicyclic hydrocarbons which contain one or more double bonds in the ring. The cyclohexadienes are not aromatic, in contrast to BENZOQUINONES which are sometimes called 2,5-cyclohexadiene-1,4-diones.

Chemicals used to destroy pests of any sort. The concept includes fungicides (FUNGICIDES, INDUSTRIAL); INSECTICIDES; RODENTICIDES; etc.

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.

An ester of phthalic acid. It appears as a light-colored, odorless liquid and is used as a plasticizer for many resins and elastomers.

Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.

A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.

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.

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.

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.

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.

An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants.

Dynamic and kinetic mechanisms of exogenous chemical and DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.

Common name for FISHES belonging to the order Perciformes and occurring in three different families.

Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.

An organochlorine insecticide whose use has been cancelled or suspended in the United States. It has been used to control locusts, tropical disease vectors, in termite control by direct soil injection, and non-food seed and plant treatment. (From HSDB)

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.

Substances or organisms which pollute the water or bodies of water. Use for water pollutants in general or those for which there is no specific heading.

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 group of FLAVONOIDS characterized with a 4-ketone.

The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)

A family of proteins involved in the transport of organic cations. They play an important role in the elimination of a variety of endogenous substances, xenobiotics, and their metabolites from the body.

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.

Non-steroidal compounds with estrogenic activity.