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 inhalation and cutaneous exposure to styrene on the drug metabolizing enzymes were studied in the rat. Rats were exposed eight hours per day, for seven successive days to 450 ppm concentration of styrene or received one cutaneous dose of styrene daily for seven consecutive days (0.5 and 3.0 g/kg). The animals were killed one day after the last dose. Styrene inhalation increased the activities of epoxide hydrase and UDPglucuronosyltransferase (4-methylumbelliferone as substrate) in liver (1.5- and 1.7-fold, respectively). Ethoxycoumarin deethylation was enhanced 1.7-fold in the kidney. The content of cytochrome P-450 in the liver and the activities of NADPH cytochrome c-reductase, benzpyrene hydroxylase and glutathione S-transferase in the liver and kidney were not altered. No changes in the enzyme activities were detected in the lung. Styrene depressed the epoxide hydrase activity in liver when administered cutaneously. No signs of enzyme induction could be seen after cutaneous administration.
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PMID:Effects of inhalation and cutaneous exposure to styrene on drug metabolizing enzymes in the rat. 62 79

The metabolic capacity of reconstituted epidermis from the outer root sheath cells of human hair follicles was determined. It was found that this epidermis possesses enzymes involved in both phase I (oxidation) and phase II (conjugation) reactions for drug biotransformation. The use of model substrates allowed the characterization of several isoenzymes. The homogenate fraction contained membrane-bound mixed-function oxydases (cytochrome P-450 dependent) involved in the O-dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzoxyresorufin, NADPH cytochrome c (P-450) reductase, testosterone 5 alpha-reductase, and UDP-glucuronosyltransferases, which conjugate 1-naphthol and bilirubin. One isoform of each glutathione S-transferase, steroid-, and arylsulfatases, acting on estrone- and 4-methylumbelliferone sulfates, was detected. Additionally, the activity of two distinct forms of epoxide hydrolases, which hydrate cis- and trans-stilbene oxides, could be measured. The presence of these drug metabolizing enzymes in the reconstituted epidermis indicates that it has a potential to serve as a model to study epidermal drug metabolism in vitro.
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PMID:Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis. 211 70

A subfraction of mitochondrial membranes was prepared from osmotically lysed rat liver mitochondria by density gradient centrifugation which contained the inner boundary membrane and the contact sites between this membrane and the outer membrane. The fraction was composed of inner and outer limiting membrane components as shown by the presence of specific marker enzymes, monoamine oxidase and glycerolphosphate oxidase. Surface proteolysis analysis, studies of cytochrome c permeability, and electron microscopy revealed the localization of the inner membrane component within a right-side-out outer membrane vesicle. Moreover, the outer membrane component in this fraction exhibited a higher capacity to bind hexokinase and had a higher specific activity of glutathione transferase than the pure outer membrane. In freeze-fracture analyses the fraction showed fracture plane deflections which may be specific for hydrophobic interactions between the two membranes.
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PMID:Enrichment and biochemical characterization of boundary membrane contact sites from rat-liver mitochondria. 301 27

The present studies were aimed at evaluating the suitability of the differentiated Reuber hepatoma cells H4IIEC3/G- for monitoring permanent damage to the DNA caused by hepatotrophic chemicals. First we determined the profile of xenobiotic metabolizing enzymes. The cells expressed various cytochrome P-450-dependent monooxygenases, UDP-glucuronosyl-, phenol sulpho- and glutathione S-transferase, cytochrome c (P-450) reductase and carboxylesterases. We then established the conditions for genotoxicity testing in H4IIEC/G- cells. Induction of resistance against 6-thioguanine and appearance of micronuclei served as indicators for mutagenicity and clastogenicity, respectively. 6-Thioguanine-resistant H4IIEC3/G- cells were phenotypically stable for at least 30 cell cycles; recovery of 6-thioguanine-resistant cells was not significantly affected by the number of cells seeded for mutant selection up to at least 10(6) cells/100-mm dish; expression time of chemically induced mutants was 12-15 days; a period of 24 h after treatment appeared to be sufficient to allow for the formation of micronuclei. Finally we tested the genotoxic effects of promutagens which are typically activated or inactivated in liver. Aflatoxin B1, N-nitrosodiethylamine and cyclophosphamide were genotoxic to H4IIEC3/G- cells at concentrations of 10-30 nM, 2-20 mM and 1 mM, respectively. N-Nitrosodimethylamine and benzo[a]pyrene were not or only weakly cytotoxic and genotoxic to the cells, but this appears most likely to be due to protective mechanisms rather than to lack of metabolic activation. The results indicate that differentiated hepatoma cells such as H4IIEC3/G- offer a means of studying the potential of chemicals for inducing permanent DNA damage in liver cells.
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PMID:Mutagenicity, clastogenicity and cytotoxicity of procarcinogens in a rat hepatoma cell line competent for xenobiotic metabolism. 304 89

In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.
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PMID:Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters. 304 47

The purpose of this work was to study the relative activities and stabilities of phase-I and phase-II drug metabolizing enzymes in incubation mixtures used in vitro genotoxicity testing in order to optimize the conditions of the assay, increase sensitivity and eliminate false negative results. Cytochrome P-450, NADPH-cytochrome P-450 (cytochrome c) reductase activity and various phase-I and phase-II enzyme activities of the drug-metabolizing system were determined in incubation mixtures used in liver microsomal assays. The behaviour of aminopyrine N-demethylase and p-nitroanisole O-demethylase activities as phase-I markers have been reported previously. Other activities measured were glutathione S-transferase, glutathione S-epoxide transferase and epoxide hydrase, and lipid peroxidation (LP) was determined. The experiments were carried out on liver S9 fractions derived from non-induced mice or mice induced with sodium phenobarbital (PB), and/or beta-naphthoflavone (beta-NF). The phase-II enzymes were much more stable (70-90% residual activity) than phase-I enzyme activities (35-60%) in all conditions tested. The residual cytochrome P-450 was approximately 70% stable and the remaining activity of NADPH-cytochrome c-reductase about 80%, indicating that this latter enzyme does not limit the rate of the monoxygenase system in these conditions. Phase-II enzymes were induced to a smaller extent (about 2 times) than in phase-I enzymes (5-6 times) by beta-NF + PB. NADPH-cytochrome c-reductase behaved as phase-II enzymes in this respect as well as for stability. LP was appreciably higher in non-induced than in induced animals. Treatment with the beta-NF + PB mixture, however, showed that induced enzymes were more stable than those obtained by simple induction with either beta-NF or PB alone. These results lead to the conclusion that prolonged incubation times in mutagenicity assays are unnecessary when considering the relative stabilities of the various phase-I and phase-II enzyme activities in the drug-metabolizing system.
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PMID:Stability of drug metabolizing enzymes during the incubation conditions of the liver microsomal assay with non-induced and induced mouse liver S-9 fractions. 311 50

Immunological indices and activity of xenobiotic metabolism enzymes in lymphocytes were studied on minipigs under normal conditions, under conditions of chronic alcoholic intoxication and after administration of anabol (an immunomodulator) to normal healthy animals and to animals with alcohol intoxication. Age-related differences with respect to the number of T-lymphocytes and activity of lymphocyte glutathione S-transferase were observed in the normal animals, the other indices such as activity of natural killer cells, K-cells, blast cell transformation with concanavalin A and activity of cytochrome c-reductase being independent of the age. Administration of anabol to healthy animals did not alter their immunoenzymatic status. Chronic alcohol intoxication was accompanied by development of secondary immune deficiency characterized by lower immunological indices and lower activity of xenobiotic metabolism enzymes in lymphocytes. Daily exposure to 0.8 g of anabol for 12 days at this background resulted in normalization of the above indices.
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PMID:[Cellular immunity and enzyme activity of xenobiotic metabolism in the lymphocytes of normal minipigs and in alcohol and anabol exposures]. 332 21

Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.
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PMID:Effect of large doses of ascorbic acid on the hepatic and extra-hepatic drug-metabolizing enzymes in guinea pig. 380 Oct 39

1. The induction of phase I and II enzymes in the liver of the male F344 rat drinking 2% (w/v) solutions of green or black tea for 6 weeks was investigated. Also studied were glutathione (GSH) and cyst(e)ine in blood, liver and kidney, as well as serum cholesterol, HDL cholesterol, triglycerides, and total and free testosterone. 2. The total carbon monoxide-discernible liver P450, b5 and NADPH-cytochrome c(P450) reductase activities were similar in all groups. 3. There were significant increases in liver of rat drinking green or black tea of P4501A1, 1A2 and 2B1 activities, but no change in P4502E1 and 3A4 activities. Of the phase II enzymes, UDP-glucuronyltransferase was increased, but glutathione S-transferase was not. 4. Serum GSH was higher in the group administered black tea, but GSH and cyst(e)ine in other groups was at control levels. Serum cholesterol was lower in rat given black compared with green tea. Triglycerides had a declining trend after green and black tea exposure compared with water controls. Free and total testosterone were not affected. 5. Thus, beverages widely used by man altered host biochemistry as regards specific phase I and II enzymes in liver of rat and specific serum parameters.
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PMID:Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. 801 87

The activities of several phase I and phase II xenobiotic-metabolizing enzymes have been measured in liver microsomes and cytosol of male rats that had been fed for 15 days with diets containing beta-carotene or canthaxanthin (300 mg/kg diet) or an excess of vitamin A (70,000 IU/kg diet), or to which beta-carotene had been administered by ip injections (7 x 10 mg/kg body weight). Microsomal cytochrome P-450 and the associated NADH- and NADPH-cytochrome c reductases were assayed, as well as several phase I and phase II enzyme activities. Phase I activities were markers of the families 1, 2, 3 and 4 of P-450; phase II activities were microsomal UDP glucuronosyl transferases (UGT) and cytosolic glutathione S-transferase (GST). Canthaxanthin accumulated in liver to a much higher level than did ingested or injected beta-carotene. Canthaxanthin increased the liver content of cytochrome P-450 (control value x 1.7), and the activity of NADH-cytochrome c reductase (x 1.5), and of some P-450-dependent enzymes (ethoxy-, methoxy-, pentoxy- and benzoxyresorufin O-dealkylases; x98, x15, x6.5 and x13, respectively), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate omega-hydroxylase). Phase II activities were also increased: UGT1 (x3.4), UGT2 (x1.2) and GST (x1.2). This induction profile, characterized by the very strong increase of the activity associated with P4501A1, and the co-induction of UGT1, closely resemble that of a classical inducer, 3-methylcholanthrene. By contrast, neither beta-carotene (fed or injected), nor an excess of vitamin A induced any significant variation of the enzyme activities measured.
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PMID:Effects of beta-carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat. 807 Jul 38


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