Glucuronides: 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.Glucuronates: 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.Glucuronosyltransferase: 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 Diphosphate Glucuronic Acid: 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.Rats, Gunn: Mutant strain of Rattus norvegicus which is used as a disease model of kernicterus.GlucuronidaseBile: 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.Metabolic Detoxication, Phase II: 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.Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.Morphine Derivatives: Analogs or derivatives of morphine.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.17-Hydroxycorticosteroids: A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Biotransformation: 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.Bilirubin: A bile pigment that is a degradation product of HEME.Quercetin: A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.Erigeron: A plant genus of the family ASTERACEAE that is similar to CONYZA. Members contain SESQUITERPENES.Bile Pigments: Linear TETRAPYRROLES that give a characteristic color to BILE including: BILIRUBIN; BILIVERDIN; and bilicyanin.Cholestanols: Cholestanes substituted in any position with one or more hydroxy groups. They are found in feces and bile. In contrast to bile acids and salts, they are not reabsorbed.Androsterone: A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.Diflunisal: A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.Xanthomatosis: A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.Stereoisomerism: 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)NitrophenolsNitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.Mefenamic Acid: A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.Sulfates: Inorganic salts of sulfuric acid.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Benzidines: Very toxic industrial chemicals. They are absorbed through the skin, causing lethal blood, bladder, liver, and kidney damage and are potent, broad-spectrum carcinogens in most species.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Flavones: A group of 4-keto-FLAVONOIDS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Hymecromone: A coumarin derivative possessing properties as a spasmolytic, choleretic and light-protective agent. It is also used in ANALYTICAL CHEMISTRY TECHNIQUES for the determination of NITRIC ACID.Microsomes: 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)Rats, Mutant Strains: Rats bearing mutant genes which are phenotypically expressed in the animals.Glucuronic Acid: A sugar acid formed by the oxidation of the C-6 carbon of GLUCOSE. In addition to being a key intermediate metabolite of the uronic acid pathway, glucuronic acid also plays a role in the detoxification of certain drugs and toxins by conjugating with them to form GLUCURONIDES.Helix (Snails): A genus of chiefly Eurasian and African land snails including the principal edible snails as well as several pests of cultivated plants.Flavanones: A group of FLAVONOIDS characterized with a 4-ketone.Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Multidrug Resistance-Associated Proteins: 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.Isoflavones: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.Estrone: An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.Propionates: Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.Tandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.Kinetics: The rate dynamics in chemical or physical systems.Molecular Structure: 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.Chromatography, Thin Layer: 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)Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Acylation: The addition of an organic acid radical into a molecule.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Drug Stability: The chemical and physical integrity of a pharmaceutical product.Isomerism: The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Cotinine: The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.Bile Acids and Salts: 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.Solid Phase Extraction: An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)ATP-Binding Cassette Transporters: 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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Benzo(a)pyrene: 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.Spectrometry, Mass, Electrospray Ionization: A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.Glycosides: Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Spectrophotometry, Ultraviolet: 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)Rats, Sprague-Dawley: 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.Carcinogens: 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.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Species Specificity: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Dogs: 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)Rats, Inbred Strains: 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.Biological Transport, Active: The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Biological Transport: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Tissue Distribution: 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.Hydrogen-Ion Concentration: 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)Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.