Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of food deprivation, carbohydrate restriction and ethanol consumption on the metabolism of eight volatile hydrocarbons (benzene, toluene, styrene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene and trichloroethylene) in rats were compared with the effects of enzyme induction by phenobarbital (PB), polychlorinated biphenyl (PCB) and 3-methylcholanthrene (MC) on the metabolism of these compounds. Although causing a marked increase both in microsomal protein and cytochrome p-450 contents, PB (80 mg/kg per day for three days) and PCB (a single dose of 500 mg/kg) induced only a limited range of enzyme activity: PB increased the metabolism of toluene, styrene, chloroform, carbon tetrachloride and trichloroethylene, and PCB only increased those of toluene, styrene and trichloroethylene. MC (20 mg/kg per day for three days) had no effect on the metabolism of any of the hydrocarbons studied. In contrast, food deprivation, carbohydrate restriction and three-week ingestion of ethanol (2.0 g/day), each enhanced the metabolism of all the hydrocarbons with little or no increase in microsomal protein and cytochrome P-450 contents. PB, PCB and MC treatments enhanced the activity of enzymes involved in conjugation reactions, UDP-glucuronyltransferase and glutathione S-transferase, whereas the dietary manipulation and ethanol consumption produced no significant effect on these enzymes. It is concluded that ethanol consumption. lowered carbohydrate intake and food deprivation affect the metabolism and toxicity of volatile hydrocarbons differently from PB, PCB or MC.
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PMID:Enhanced metabolism of volatile hydrocarbons in rat liver following food deprivation, restricted carbohydrate intake, and administration of ethanol, phenobarbital, polychlorinated biphenyl and 3-methylcholanthrene: a comparative study. 392 Aug 36

Donryu strain albino rats were maintained on a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for nine successive generations. Some rats in the fourth to eighth generations showed marked resistance to the carcinogenic action of 3'-Me-DAB. In the liver where we found tumors, their size and number are smaller than in the corresponding original strain of rats fed on a diet containing 3'-Me-DAB. No significant differences were found in the total cytochrome P-450 contents or epoxide hydrolase activities of the livers of the resistant variant and the original strain, but the benzo(a)pyrene hydroxylase activity which is mainly attributed to cytochrome P-448 and glutathione S-transferase activity of the resistant variant were lower. The inductions of hepatic cytochrome P-488 and benzo(a)pyrene hydroxylase on administration of polychlorinated biphenyls or 3-methylcholanthrene were also lower in the resistant rats. In the mutagenicity test on Salmonella typhimurium TA 98 the liver 9000 X g supernatant fraction from 3'-Me-DAB-resistant F7 rats did not fully induce the mutagenicities of 3'-Me-DAB and several other carcinogens. Thus the resistance of F7 rats to the chemical carcinogen may be related to the lower activities of some drug-metabolizing enzymes and the poor inducibility of cytochrome P-448 in their liver, although selection of resistant rats should be continued for further generations before coming to a definite conclusion on biochemical basis of apparent resistance to 3'-Me-DAB.
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PMID:Comparison of drug-metabolizing activities in the livers of carcinogen-sensitive parent rats and carcinogen-resistant descendants. 393 22

The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene.
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PMID:Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats. 401 64

The mechanism of the protective action of methionine and N-acetylcysteine against the toxicity of paracetamol was investigated in vivo. N-acetylcysteine inhibited the O-deethylation of ethoxyresorufin (cytochrome P-448) while methionine enhanced the N-demethylation of benzphetamine (cytochrome P-450) and increased hepatic microsomal levels of cytochrome P-450. These observations indicate that N-acetylcysteine, but not methionine, could afford protection against paracetamol hepatotoxicity, at least partly, by inhibiting cytochrome P-448 activity and thus the generation of the reactive intermediate. However, previous studies demonstrating no decrease in the urinary excretion of glutathione conjugates of paracetamol (derived from the reactive intermediate) in animals treated with N-acetylcysteine suggest that this is unlikely to be the prevailing mechanism of action. Administration of a large dose of paracetamol, as expected, depleted glutathione levels and inhibited cytosolic glutathione transferase activity. Administration of either N-acetylcysteine or methionine 1 h after paracetamol prevented both effects. On the basis of the present work and previously published observations, it is concluded that the major mechanism of action of N-acetylcysteine and methionine in vivo is by acting as precursors of intracellular glutathione.
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PMID:Mechanism of the protective action of n-acetylcysteine and methionine against paracetamol toxicity in the hamster. 406 51

NADPH-cytochrome c reductase, cytochrome -450, benzo[a]pyrene mono-oxygenase, epoxide hydratase, and glutathione S-transferase activities in the liver of the Northern pike (Esox lucius) have been measured and partially characterized. The level of these systems in pike liver is between 13.2 and 133% of the corresponding levels in rat liver, with the exception of glutathione S-transferase, whose specific activity in the high-speed supernatant fraction of pike liver is 305% of that in rat liver. In addition, pike liver contains about 23% of the mammalian level of reduced glutathione. Drug-metabolizing systems in pike liver are distributed in essentially the same manner in subfractions as the corresponding systems in the liver of mammals. Benzo[a]pyrene mono-oxygenase and epoxide hydratase activities display the expected pH maxima of 7.5 and 9.5, respectively, and have temperature maxima of 37 degrees and 47 degrees C, respectively. NADPH-cytochrome c reductase and glutathione S-transferase activities are relatively independent of temperature. Intraperitoneal treatment of Northern pike with methylcholanthrene induces the benzo[a]pyrene mono-oxygenase activity of liver microsomes 33-fold.
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PMID:Initial characterization of drug-metabolizing systems in the liver of the Northern pike, Esox lucius. 610 96

This article is a summary of laboratory methods for the hepatic drug metabolizing enzymes which are reliable, sensitive, and reasonably straightforward to perform. Assay conditions are given for which the enzyme rate determinations are linear with respect to time and protein concentration for hepatic tissue preparations from Charles River Sprague Dawley CD male rats. In selecting these particular assay methods, factors such as disposal of radioactive wastes, safety of laboratory personnel, and cost of required equipment were considered. Thus 9 of the 10 hepatic parameters utilize simple spectrophotometric techniques; the remaining assay (ethoxyresorufin O-deethylase) requires a spectrophotofluorometer. The hepatic toxification/detoxification assays are cytochrome P-450 and reduced glutathione content, NADPH-cytochrome C reductase, aminopyrine N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase (3 substrates) and UDP-glucuronyltransferase (2 substrates).
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PMID:Laboratory methods for ten hepatic toxification/detoxification parameters. 642 71

The metabolism of the carcinogenic and adrenocorticolytic polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene in rat adrenals was investigated. Both 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene, which also is a well-known carcinogen but has no short-term effects on rat adrenals, appear to be metabolized by one common type of cytochrome P-450-dependent monooxygenase localized in the endoplasmic reticulum. Studies of the kinetic properties of this cytochrome P-450 reveal that the Km values for 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene are lower than 3 microM. Identification of metabolites indicates that, with both 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene, phenols and diols were formed the relative rates of formation of which were markedly influenced by the expoxide hydrase inhibitor cyclohexane oxide, suggesting that epoxides are intermediate metabolites. Added or endogenous microsomal glutathione S-transferase B had little or no effect on the distribution of metabolites. A rather selective binding of metabolites of 7,12-dimethylbenz(a)anthracene to soluble and microsomal proteins was demonstrated. The adrenal cytochrome P-450 involved in the conversion of these polycyclic aromatic hydrocarbons appears to be unrelated to those responsible for the synthesis of mineralocorticoids and glucocorticoids from cholesterol. Among androgens and estrogens, estradiol proved to be the most inhibitory steroid, suggesting a role of the hydrocarbon-metabolizing cytochrome P-450 in estrogen biosynthesis. However, no such function could be demonstrated conclusively. The metabolite patterns and the effects of nonsteroid inhibitors of liver monooxygenases, e.g., alpha-naphthoflavone, SU 9055, and ellipticine, suggest that the properties of this cytochrome P-450 resemble those of the 3-methyl-cholanthrene-inducible cytochrome P-488 from rat liver.
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PMID:Metabolism of polycyclic aromatic hydrocarbons and covalent binding of metabolites to protein in rat adrenal gland. 680 Jun 53

Cytochrome P 450 concentration, related monooxygenase activities (towards aniline, p-nitroanisole, benzphetamine, ethoxycoumarin, benzo(a)pyrene, testosterone, and dehydroepiandrosterone), epoxide hydrolase, and glutathione S-transferase activities were measured in the liver of human foetuses aged from 15 to 38 weeks and compared to adult activities. Different ontogenic patterns seem to exist between monooxygenase activities: if the overall cytochrome P 450 concentration, aniline hydroxylase, benzphetamine demethylase, epoxide hydrolase, and glutathione S-transferase activities reach about the half of adult values as early as 15-25 weeks of gestational age, the metabolism of benzo(a)pyrene, ethoxycoumarin, and testosterone in position 6 beta is very low in these foetuses, whereas the 16 alpha hydroxylation of dehydroandrosterone is higher than in adult human liver. Foetal and adult cytochromes P 450 were resolved by DEAE cellulose chromatography into three different fractions: in reconstitution experiments, the major fraction (A) was active toward aniline, whereas benzphetamine and ethoxycoumarin were mainly metabolized by the two other fractions (Ba and Bb). Results show that multiple cytochromes 450 are present in foetal liver and are able to catalyze, with a lower molecular activity, the same reactions as in adult human liver.
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PMID:Drug-metabolizing enzymes in human foetal liver: partial resolution of multiple cytochromes P 450. 716 74

Because of the interest in male reproductive tract toxicity, we determined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-450 levels and the specific activity of aryl hydrocarbon hydroxylase (AHH), epoxide hydrase and glutathione S-transferase in the rat prostate glands after a single oral dose of TCDD (10 microgram/kg b.wt.). The maximum induction of AHH activity and cytochrome P-450 levels in the prostate glands was approximately 200- and 6.5-fold that of controls. After TCDD treatment, the peak induction of AHH activity and cytochrome P-450 levels in the prostate glands was observed at 16 and 48 hr, respectively; however, the specific activity of epoxide hydrase or glutathione S-transferase in prostate glands was not induced at any time after TCDD treatment. TCDD-induction of AHH and cytochrome P-450 contents can be completely inhibited by a single pretreatment with either actinomycin D or cycloheximide, suggesting TCDD induces de novo synthesis of specific proteins. Dramatic increases in AHH activity (200-fold increase) were associated with the new formation of cytochrome P-450 in the rat prostate glands after a single oral dose of TCDD. The biological significance of such a dramatic increase of prostatic AHH activity and the emergence of new cytochrome P-446 in rat prostate glands is unknown at the present time.
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PMID:Induction of aryl hydrocarbon hydroxylase activity in the rat prostate glands by 2,3,7,8-tetrachlorodibenzo-p-dioxin. 744 19

The effects of the synthetic dibromo-pyrethroid insecticide deltamethrin on some hepatic phase I and II enzyme activities were studied in rat liver. The animals were treated with daily doses of 5 and 10 mg/kg of both pure insecticide or its commercial formulation (Decis), administered i.p. in corn oil for 7 days. The following enzyme activities were studied: NADPH-cytochrome-P450 reductase, aryl-hydrocarbon hydroxylase, aminopyrine N-demethylase, glutamyl cysteine synthetase, glutathione S-transferase, glutathione peroxidase, peroxisomal acyl-CoA oxidase, catalase, and urate oxidase. Both deltamethrin and its commercial formulation were effective in modifying the activities of several of these hepatic xenobiotic-metabolizing enzymes. However, some differences in enzyme modifications were found between treatment with pure or commercial deltamethrin, the latter being more active. This effect could be ascribed to additives, solvents, and chemical intermediates present in the Decis formulation. These results suggest that exposure to this deltamethrin commercial formulation could be more dangerous than exposure to deltamethrin alone, both in terms of its hepatotoxicity and/or alterations in the hepatic biotransformation of other occupational/environmental xenobiotics.
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PMID:Studies on hepatic xenobiotic-metabolizing enzymes in rats treated with insecticide deltamethrin. 747 74


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