Loading...
Bithionol: Halogenated anti-infective agent that is used against trematode and cestode infestations.Thymol: A phenol obtained from thyme oil or other volatile oils used as a stabilizer in pharmaceutical preparations, and as an antiseptic (antibacterial or antifungal) agent. It was formerly used as a vermifuge.Metabolic Detoxication, Drug: 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.Metabolic Detoxication, Phase I: 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.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.Glutathione Transferase: 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.Psychoses, Alcoholic: A group of mental disorders associated with organic brain damage and caused by poisoning from alcohol.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.Aristolochic Acids: Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).Adrenochrome: Pigment obtained by the oxidation of epinephrine.Aflatoxin B1: 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.Aminopyrine N-DemethylaseCytochrome P-450 CYP1A1: 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.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.NAD(P)H Dehydrogenase (Quinone): 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.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.Glutathione: 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.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Anticarcinogenic Agents: Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans.Thiocyanates: Organic derivatives of thiocyanic acid which contain the general formula R-SCN.Cytochrome P-450 Enzyme System: 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.Carboxylesterase: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Isothiocyanates: Organic compounds with the general formula R-NCS.Enzyme Induction: 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.PyrazinesCarboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Oxidation-Reduction: 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).Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Rats, Inbred F344Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Kinetics: The rate dynamics in chemical or physical systems.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.