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 placenta possesses the ability to metabolize numerous xenobiotics and endogenous steroids. However, it is unknown whether regional differences in these enzymatic reactions exist in the human placenta. To this end, we undertook a study of four regions of the placenta, the chorionic plate, maternal surface, placental margin and whole tissue, to assess the activities of cytochrome P450 1A1 and 19A1 (aromatase) and glutathione S-stransferase in these fractions. No differences in either P450 1A1 or glutathione S-transferase activities were noted among any of the placental fractions. However, with respect to P450 19A1 activity, the placental margin differed significantly from all other fractions (p < 0.05). This study demonstrates that whole tissue samples of the human placenta are adequate for placental cytochrome P450 and glutathione S-transferase metabolism studies.
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PMID:Regiospecificity of placental metabolism by cytochromes P450 and glutathione S-transferase. 893 64

Effects of continuous feeding flavonoids (flavone, flavanone, and tangeretin) on drug-metabolizing enzymes in rat liver were investigated to ascertain how long feeding is required to reach maximal induction and to determine whether maximal induction is maintained for a long period of feeding. In the first experiment rats received a diet containing 10 mmol flavonoid/kg dry matter for 4, 8, 16, or 32 d. The second experiment was designed to examine the time course for induction during the first 4 d. The kinetics of induction depended on the chemical structure of the flavonoid and was different from one enzyme to another. Flavone increased P450 1A and P450 2B apoproteins and stimulated many enzyme activities. A significant increase of P450 1A1/2 proteins, ethoxyresorufin O-deethylase (EROD), and methoxyresorufin O-demethylase (MROD) activities occurred as early as 6 h after the first administration, and a gradual increase was observed up to 4 d of feeding. P450 2B1/2 proteins and pentoxyresorufin O-depentylase (PROD) activity were also increased but after a lag period when compared with P450 1A1/2 proteins. EROD and MROD activities declined after 4 d, whereas PROD activity remained steady during 32 d of flavone feeding. Glutathione transferase (GST) and p-nitrophenol UDP-glucuronosyl transferase (UGT) activities were also increased. The maximal induction was reached by 4 d of feeding for UGT and after a longer duration of feeding (16 d) for GST. Flavanone treatment induced mostly P450 2B1/2 proteins and PROD, GST, and UGT activites. After 4 d of feeding, P450 2B1/2 proteins and PROD activity declined whereas GST and UGT activities remained steady. Tangeretin treatment produced changes similar to flavone but of lesser magnitude and after a longer delay.
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PMID:Time course of induction of rat hepatic drug-metabolizing enzyme activities following dietary administration of flavonoids. 896 9

These studies examined the ability of garlic powder or allyl sulfur compounds to modify selenite protection against 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary epithelial cell DNA adducts. In Study 1, female rats (n = 5) were fed diets containing sodium selenite at 0.1, 0.5, or 1.0 mg Se/kg and garlic powder at 0, 20, or 40 g/kg diet. Total DNA adducts correlated inversely with selenite or garlic powder intake. Garlic powder enhanced the selenite inhibition of mammary DNA adducts. In Study 2, selenite (2.0 mg Se/kg diet), garlic powder (20 g/kg diet), water-soluble S-allyl cysteine (SAC; 5.2 mumol/kg diet), and oil-soluble diallyl disulfide (DADS; 5.2 mumol/kg diet) inhibited (p < 0.05) total DNA adducts by 45%, 40%, 80%, and 75%, respectively. Combining selenite with garlic powder, SAC, or DADS further inhibited DNA adducts. Selenite, but not garlic powder, SAC, or DADS, enhanced liver glutathione S-transferase and uridine diphosphate-glucuronosyltransferase activities. Selenite, garlic powder, SAC, or DADS did not affect liver cytochrome P-450 1A1 activities. The present studies provide evidence that synergistic protection against the initiation of DMBA carcinogenesis occurs when selenite is supplemented in conjunction with garlic or its allyl sulfur components.
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PMID:Garlic powder and allyl sulfur compounds enhance the ability of dietary selenite to inhibit 7,12-dimethylbenz[a]anthracene-induced mammary DNA adducts. 912 44

This report describes the establishment and characterization of the mhPKT cell line derived from the liver of a transgenic mouse harboring the simian virus (SV40) large T and small t antigens placed under the control of the 5' regulatory sequence of the rat L-type pyruvate kinase (L-PK) gene. mhPKT cells had a prolonged life span, expressed the SV40-encoded nuclear large T antigen when grown in glucose-enriched medium, and induced tumors when injected subcutaneously into athymic (nu-nu) mice. Growth on petri dishes or filters yielded multiple layers of cuboid cells, with numerous spaces between adjacent cells that were closed by junctional complexes. These bile canaliculi-like structures exhibited numerous microvilli in which villin, an actin-binding brush-border protein, colocalized with actin. These bile canaliculi-like structures appeared to be functional as they accumulated fluorescein. mhPKT cells conserved the expression of the liver-specific transcription factors HNF1, HNF3, HNF4, and DBP together with substantial levels of L-PK and albumin but not alpha-fetoprotein mRNA transcripts. mhPKT cells mainly metabolized testosterone into androstenedione and 6beta-hydroxytestosterone, as in vivo. 3-Methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) markedly increased ethoxyresorufin-O-deethylase activity and the related cytochrome P450 (CYP) 1A1/2 protein, whereas alpha-naphtoflavone antagonized the TCDD-elicited induction. Phenobarbital slightly increased the CYP2B-mediated activities of pentoxyresorufin-O-depentylase, 2beta- and 16beta-testosterone hydroxylase. mhPKT cells also had substantial sulfotransferase, UDP-glucuronyltransferase, and glutathione S-transferase activities. This model may serve as a tool for long-term in vitro studies of xenobiotic metabolism, potent CYP inducers, and hepatocyte damage due to drugs and other factors.
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PMID:Activity and inducibility of drug-metabolizing enzymes in immortalized hepatocyte-like cells (mhPKT) derived from a L-PK/Tag1 transgenic mouse. 926 Sep 6

Previous research showed that treatment with selenium-enriched garlic (Se-garlic) was able to inhibit the initiation phase of mammary carcinogenesis in the dimethyl-benz[a]anthracene (DMBA) model in rats. The present study was designed to investigate the following parameters: 1) DMBA-DNA adduct formation in liver and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase II xenobiotic-metabolizing enzymes, and 4) tissue selenium levels as a function of Se-garlic supplementation. Prior feeding with an Se-garlic-containing diet (at 3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in liver and mammary gland. This was accompanied by a 40% increase in urinary excretion of DMBA metabolites over a two-day period. Several liver P-450 enzymes were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared with controls receiving 0.1 ppm Se, no significant alteration in activity was detected with respect to P-450 1A1 (responsible for DMBA activation), 1A2, 2B1, 2E1, and 3A4. In contrast, glutathione S-transferase and uridine 5'-diphosphate-glucuronyltransferase activities were elevated to a maximum of 2- to 2.5-fold in liver and kidney. As expected, there was a dose-dependent elevation of selenium concentrations in liver, kidney, mammary gland, and plasma as a function of the level of Se-garlic supplementation. Our data seem to suggest that an increased detoxification of carcinogen via the phase II conjugating enzymes might represent a mechanism of tumor suppression by Se-garlic.
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PMID:Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats. 929 Jan 26

To examine whether oxfendazole has tumour-promoting activity, a total of 100 male Fisher 344 rats were initiated with a single ip injection of 100 mg/kg of diethylnitrosamine (DEN) or given saline vehicle alone and starting 1 wk later given diet containing 500, 250, 100, 10 or 0 ppm of oxfendazole for 8 wk. Sub-groups of five rats each from the DEN plus 250 and 0 ppm groups were killed after wk 1 of oxfendazole treatment and the remaining animals at wk 8. At the termination relative liver weights were significantly increased in the DEN-initiated and non-initiated groups treated with 250 ppm and 100 ppm or more, respectively, compared with the corresponding controls values. Light microscopical examination showed centrilobular hepatocellular hypertrophy in all animals receiving 100 ppm or more. Electron microscopy also revealed marked increases in smooth endoplasmic reticulum in hepatocytes of the DEN plus 500 ppm group. Furthermore, induction of cytochrome P-450 (CYP) 1A1/2, 2B1/2 or 4A1 was observed in the DEN plus 100 ppm group, that of CYP 1A1/2 being most marked. A similar change in CYP 1A1/2 was seen in the DEN plus 10 ppm group. The numbers and areas of connexin 32 (Cx32)-positive spots per hepatocyte were also significantly decreased in a dose-dependent manner. Similar changes in liver weights, P-450 isozymes and Cx32 immunohistochemistry were already evident in the DEN plus 250 ppm group at wk 1. The number of placental form glutathione S-transferase positive single cells was significantly increased in the DEN-initiated groups treated with 250 ppm or more. The results therefore strongly suggest that oxfendazole exerts liver tumour promotion potential.
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PMID:Liver tumour-promoting effects of oxfendazole in rats. 935 Feb 25

The effects of motorcycle exhaust (ME) on cytochrome P-450 (P-450)-dependent monooxygenases were determined using rats exposed to the exhaust by either inhalation, intratracheal, or intraperitoneal administration. A 4-wk ME inhalation significantly increased benzo[a]pyrene hydroxylation, 7-ethoxyresorufin O-deethylation, and NADPH-cytochrome c reductase activities in liver, kidney, and lung microsomes. Intratracheal instillation of organic extracts of ME particulate (MEP) caused a dose- and time-dependent significant increase of monooxygenase activity. Intratracheal treatment with 0.1 g MEP extract/kg markedly elevated benzo[a]pyrene hydroxylation and 7-ethoxyresorufin O-deethylation activities in the rat tissues 24 h following treatment. Intraperitoneal treatment with 0.5 g MEP extract/kg/d for 4 d resulted in significant increases of P-450 and cytochrome b5 contents and NADPH-cytochrome c reductase activity in liver microsomes. The intraperitoneal treatment also markedly increased monooxygenases activities toward methoxyresorufin, aniline, benzphetamine, and erythromycin in liver and benzo[a]pyrene and 7-ethoxyresorufin in liver, kidney, and lung. Immunoblotting analyses of microsomal proteins using a mouse monoclonal antibody (Mab) 1-12-3 against rat P-450 1A1 revealed that ME inhalation, MEP intratracheal, or MEP intraperitoneal treatment increased a P-450 1A protein in the hepatic and extrahepatic tissues. Protein blots analyzed using antibodies to P-450 enzymes showed that MEP intraperitoneal treatment caused increases of P-450 2B, 2E, and 3A subfamily proteins in the liver. The ME inhalation, MEP intratracheal, or MEP intraperitoneal treatment resulted in significant increases in glutathione S-transferase activity in liver cytosols. The present study shows that ME and MEP extract contain substances that can induce multiple forms of P-450 and glutathione S-transferase activity in the rat.
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PMID:Effects of motorcycle exhaust on cytochrome P-450-dependent monooxygenases and glutathione S-transferase in rat tissues. 972 77

This study compared catalytic and immunochemical properties of drug metabolizing phase I and II enzyme systems in houbara bustard (Chlamydotis undulata) liver and kidney and rat liver. P450 content in bustard liver (0.34 +/- 0.03 nmol mg-1 protein) was 50% lower than that of rat liver (0.70 +/- 0.02 nmol mg-1 protein). With the exception of aniline hydroxylase activity, monooxygenase activities using aminopyrine, ethoxyresorufin and ethoxycoumarin as substrates were all significantly lower than corresponding rat liver enzymes. As found in mammalian systems the P450 activities in the bird liver were higher than in the kidney. Immunohistochemical analysis of microsomes using antibodies to rat hepatic P450 demonstrated that bustard liver and kidney express P4502C11 homologous protein; no appreciable cross-reactivity was observed in bustards using antibodies to P4502E1, 1A1 or 1A2 isoenzymes. Glutathione content and glutathione S-transferase (GST) activity in bustard liver were comparable with those of rat liver. GST activity in the kidney was 65% lower than the liver. Western blotting of liver and kidney cytosol with human GST isoenzyme-specific antibodies revealed that the expression of alpha-class of antibodies exceeds mu in the bustard. In contrast, the pi-class of GST was not detected in the bustard liver. This data demonstrates that hepatic and renal microsomes from the bustard have multiple forms of phase I and phase II enzymes. The multiplicity and tissue specific expression of xenobiotic metabolizing enzymes in bustards may play a significant role in determining the pharmacokinetics of drugs and susceptibility of the birds to various environmental pollutants and toxic insults.
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PMID:Drug metabolizing enzyme systems in the houbara bustard (Chlamydotis undulata). 982 52

Urinary naphthols, 1- and 2-naphthol, recently have been suggested as route-specific biomarkers for exposure to airborne polycyclic aromatic hydrocarbons. For the proper application of urinary naphthols as biomarkers, we studied effects of lifestyle on urinary naphthols levels in 119 Japanese male workers. After improving the detection limit of urinary naphthols up to 0.27 microg/L by high-resolution capillary gas chromatography/mass spectrometry/selected ion monitoring, urinary naphthols were detectable in approximately 90% of the subjects. Among detectable samples, the geometrical mean (GM) of urinary 1-naphthol concentration was 5.13 microg/L (geometrical standard deviation, GSD, 4.90), while the GM of urinary 2-naphthol concentration was 3.16 microg/L (GSD, 5.61). We observed that urinary 1- and 2-naphthol level were three- and sevenfold higher, respectively, among smokers than among nonsmokers (p < 0.01). The ratios of urinary 2-naphthol to 1-naphthol were significantly higher among smokers than nonsmokers (p < 0.05). The number of cigarettes smoked and urinary cotinine levels were also positively related to the concentration of urinary naphthols (p < 0.01), while other lifestyle factors, i.e., age and consumption of alcohol, greasy or salty food, sweets, fruits, vegetables, meat, or fish, were not. We also studied whether genetic polymorphisms of enzymes, which were involved in naphthalene metabolism, affected urinary naphthols levels. The cytochrome P450 (CYP) 1A1 exon 7 genetic polymorphism was not related to urinary naphthol levels. Among smokers, the subjects with c1/c2 or c2/c2 type of CYP2E1, which was determined by CYP2E1 RsaI polymorphism in 5'-flaking region, showed higher concentrations of urinary 2-naphthol than the subjects with c1/c1 type regardless of creatinine-correction (p < 0.05) and the subjects with glutathione S-transferase (GST) M1 deficient type showed higher concentrations of both urinary 1- and 2-naphthol than those with GSTM1 normal type but only without creatinine-correction (p < 0.05). Thus, when urinary naphthols are used as biomarkers, smoking and the genetic polymorphisms of CYP2E1 and GSTM1 should be considered.
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PMID:A study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons. 982 67

The risk of lung and urinary bladder cancers was reported to be increased in individuals who carried high risk genotypes in either cytochrome P450 (CYP)1A1, CYP2E1 or glutathione S-transferase (GST)M1, and the combined genotype of both CYP1A1 and GSTM1 enzymes have an enhanced tendency of risk to lung cancer more significantly. On the other hand, gene-environmental interactions have to be considered precisely, and are indicated to be more pronounced at lower levels of cigarette exposure in which the susceptibility to lung cancer increased in the case of individuals with some mutated alleles. In each category, however, there are several confused and controversial results. These early predictions of genetic disposition for the incidence of such severe disease as cancer may prompt them to receive early examination and diagnosis and to expect a complete cure from the diseases for their life.
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PMID:Polymorphic CYP genes and disease predisposition--what have the studies shown so far? 1002 50


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