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)

Marsupials and eutherians display vastly different reproductive strategies. Marsupials are characterised by the production of altricial neonates with little functional capacity. An investigation of the ontogenic expression of phase I (mixed function oxidase) and phase II (glutathione transferase) enzyme systems in the marsupial, the brushtail possum was undertaken. Enzyme expression in the youngest age group studied (60 days old) was between 5% and 10% of the adult level. A gradual increase in expression was then observed until a significant 3-fold increase to adult levels of expression of cytochrome P450, cytochrome b5 and glutathione transferase content and ECOD and AE activity was observed in brushtail possum young between the ages of 150 +/- 15 and 180 +/- 15 days. The expression of EROD activity reached adult levels by the age of 150 +/- days, while the expression of NADPH-cytochrome c reductase activity was delayed and adult levels had not yet been achieved by the oldest group studied (> 200 days). The ontogenic expression of detoxication enzymes was significantly delayed in the marsupial in comparison to eutherians. Adult levels were achieved during the weaning period, suggesting that dietary xenobiotics act as a regulatory mechanism in the developmental expression of these enzymes in the brushtail possum.
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PMID:Ontogenic expression of detoxication enzymes in an Australian marsupial, the brushtail possum (Trichosurus vulpecula). 941 14

The present study evaluates the postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit extract via assessing the modulation in the biotransformation system enzymes of suckling neonates and lactating mice. The peel, seed or whole fruit extract of Momordica (100 microl/animal/day) independently induced a significant increase in the hepatic levels of glutathione S-transferase (GST) and acid soluble sulfhydryl (-SH) after 14 or 21 days treatment in lactating dams (P < 0.01) and translactationally exposed neonates (P < 0.05). However, the elevation (P < 0.05) in hepatic cytochrome b5 (Cyt. b5) and cytochrome P-450 (Cyt. P-450) levels was observed only in the lactating dams treated with the respective extracts of peel, seed or whole fruit of Momordica. In lactating dams and suckling neonates the modulated levels of biotransformation system enzymes suggest the potential for the translactational passage of active principle(s) and/or metabolites of Momordica.
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PMID:Postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit extract in the detoxication pathway of suckling neonates and lactating mice. 946

Most carcinogens and xenobiotics are metabolized primarily by the mixed function oxidase system which includes cytochrome P450, cytochrome b5, NADPH-cytochrome c reductase and aryl hydrocarbon [benzo(a)pyrene] hydroxylase. The present study investigates the influence of infection with different levels of Schistosoma mansoni cercariae on the hepatic levels of reduced glutathione, glutathione S-transferase and glutathione reductase in addition to the enzymes of mixed function oxidase. Cercariae infection levels of 60, 120, 180, 300 and 600 per mouse increased: (i) the hepatic content of cytochrome P450 by 27%, 38%, 72%, 57%, 48% respectively; (ii) the aryl hydrocarbon hydroxylase activity by 44%, 64%, 76%, 90%, 51% respectively; and (iii) the hepatic level of reduced glutathione by 67%, 83%, 103%, 60%, 38% respectively. The cytochrome b5 content did not change at the lowest level of infection but increased at the other four levels by 45%, 76%, 49% and 38% respectively. The activity of glutathione S-transferase increased at the first three levels by 42%, 40%, 27% respectively and decreased at the last two levels by 28% and 52% respectively. On the other hand, the activity of glutathione reductase did not change at any level, whereas, NADPH-cytochrome c reductase activity decreased at the last two levels by 44% and 54%. The alterations in the activities of phase I & II of drug-metabolizing enzymes as a result of infection with different levels of S. mansoni may thus change the liver's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of aromatic hydrocarbons, e.g. benzo(a)pyrene, upon the liver and probably other organs. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.
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PMID:Different levels of Schistosoma mansoni infection induce changes in drug-metabolizing enzymes. 963 5

This study evaluates the potential for the perinatal transfer of active constituents and/or metabolites of Chlorella vulgaris (E-25) via modulating the hepatic level of drug metabolizing enzymes and lipid peroxidation. E-25 (100, 300 or 500 mg/kg b.w./day) induced a significant increase in the hepatic levels of glutathione S-transferase (GST) and sulfhydryl (-SH) in fetal and neonatal systems after 14 days treatment to gestating or lactating mice. E-25 (500 mg/kg b.w./day)-modulated inhibition of cytochrome b5 (Cyt. b5), cytochrome P-450 (Cyt. P-450) and malondialdehyde (MDA) level was observed in the fetal and neonatal hepatic tissue following the transplacental or translactational exposure. The observed modulation in the levels of hepatic drug metabolizing enzymes and lipid peroxidation suggest the chemopreventive potential of E-25 via perinatal passage of active constituents and/or metabolites.
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PMID:Perinatal influence of Chlorella vulgaris (E-25) on hepatic drug metabolizing enzymes and lipid peroxidation. 967 62

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

The present study was designed to elucidate the mechanistic inhibitory efficacy of clocimum (an eugenol rich variety of Ocimum gratissimum; Labiatae) oil on murine skin papillomagensis. Topical application of clocimum oil (50 microl/animal/day) during peri-initiation stage (1 week before and 2 weeks after initiation) of 7,12-dimethylbenz[a]anthracene (DMBA)-induced papillomagenesis and/or during the tumour promotion stage reduced (P < 0.05) the (i) tumour burden to 5.00, 4.41 and 4.50 (positive control value 5.27); (ii) cumulative number of papillomas to 85, 75 and 72 (positive control value : 95); and (iii) percent incidence of mice bearing papillomas to 94, 89 and 88, respectively (positive control value 94). Significant (P < 0.01) elevation in the hepatic levels of glutathione S-transferase (GST), sulfhydryl (-SH) and cytochrome b5 (Cyt. b5) was observed by the respective topical treatment of clocimum oil. Even in the skin tissue of the mouse, the topical treatment of clocimum oil enhanced (P < 0.05) the -SH content. The results suggest the modest chemopreventive potential of clocimum oil against the murine skin papillomagenesis, and such effects may be partly due to the modulated xenobiotic detoxication system enzymes.
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PMID:Modulatory potential of clocimum oil on mouse skin papillomagenesis and the xenobiotic detoxication system. 1047 35

Mice were fed with high zinc diet (15 g/kg) for 3 weeks. High zinc could cause liver toxicity: 1. inhibiting the activity of GOT and GPT in liver homogenate, reducing GSH and glycogen contents. 2. increasing the activity of aniline hydroxylase and inhibiting the activities of NADPH-cytochrome C reducease, benzo-phytamine-N-demethylase and glutathione S-transferase. The activities of cytochrome P450 and cytochrome b5 were not obviously changed 3. increasing microsomal membrane fluidity in the superficial layers, but not in the deep layers.
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PMID:[Effects of high dietary zinc on liver function, hepatic drug metabolism enzymes and membrane fluidity in mice]. 1068 26

The present study assesses the potential of arecoline alkaloid, by direct exposure in lactating dams and translactational exposure in neonates, to modulate the efficacy of clocimum oil as a blocking agent in chemopreventive pathway. Clocimum oil (25 or 50 microl/dam/day) induced a significant increase in the hepatic levels of phase II glutathione S-transferase (GST) and acid-soluble sulfhydryl in lactating dams and suckling neonates while the elevated levels of hepatic phase I cytochrome b5 (Cyt. b5) and cytochrome P-450 (P450) were observed only in the dams. Arecoline (0.6 mg/dam/day) alone did not modulate the hepatic GST and sulfhydryl levels in either dams or pups, although significant induction was observed in the hepatic levels of Cyt. b5, P450 and malondialdehyde (MDA) in lactating dams and suckling neonates. Clocimum oil-modulated hepatic levels of phase II components were depressed whereas phase I enzymes and lipid peroxides levels were further elevated by clocimum oil-plus-arecoline treatment. The direct or translactationally augmented levels of bioactivated species of the administered compounds, via enhanced phase I oxidative catalysis and less efficient GST/GSH conjugational detoxication, may suggest the antagonistic influence of arecoline on chemopreventive efficacy of clocimum oil.
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PMID:Direct and translactational effect of arecoline alkaloid on the clocimum oil-modulated hepatic drug metabolizing enzymes in mice. 1094 24

The effect of hydroalcoholic (80% ethanol, 20% water) extract of leaves of Aegle marmelos was examined on carcinogen-metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation, using two doses of dried extract (50 and 100 mg kg(-1) daily for 14 days), in the liver of mice. The modulatory effect of the extract was also examined on extrahepatic organs (lung, kidney and fore-stomach) for effects on the activity of glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase. Extract treatment significantly increased the basal levels of acid-soluble sulphydryl (-SH) content, cytochrome P450, NADPH-cytochrome P450 reductase, cytochrome b5, NADH-cytochrome b5 reductase, glutathione S-transferase, DT-diaphorase, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver. Aegle acted as a bifunctional inducer since it induced both phase-I and phase-II enzyme systems. Both doses significantly decreased the activity of lactate dehydrogenase and formation of malondialdehyde in liver, suggesting a role in cytoprotection as well as protection against pro-oxidant-induced membrane damage. Butylated hydroxyanisole (positive control) induced almost all the antioxidative parameters measured in this study. The extract was effective in inducing glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase in lung, glutathione S-transferase, DT-diaphorase and superoxide dismutase in fore-stomach, and DT-diaphorase and superoxide dismutase in lung. These significant changes in the levels of drug-metabolizing enzymes and antioxidative profiles are strongly indicative of the chemopreventive potential of this plant, especially against chemical carcinogenesis.
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PMID:Effect of Aegle marmelos on biotransformation enzyme systems and protection against free-radical-mediated damage in mice. 1100 71

The effect of two different doses (50 and 100 mg/kg body wt/day for 14 days) of 80% ethanolic extract of the leaves of Adhatoda vesica were examined on drug metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 8 weeks old Swiss albino mice. The modulatory effect of the extract was also examined on extra-hepatic organs viz. lung, kidney and forestomach for the activities of glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase. Significant increase in the activities of acid soluble sulfhydryl (-SH) content, cytochrome P450, NADPH-cytochrome P450 reductase, cytochrome b5, NADH-cytochrome b5 reductase, glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were observed in the liver at both dose levels of treatments. Adhatoda vesica acted as bifunctional inducer since it induced both phase I and phase II enzyme systems. Both the treated groups showed significant decrease in malondialdehyde (MDA) formation in liver, suggesting its role in protection against prooxidant induced membrane damage. The cytosolic protein was significantly inhibited at both the dose levels of treatment indicating the possibility of its involvement in the inhibition of protein synthesis. BHA has significantly induced the activities of GR and GSH in the present study. The extract was effective in inducing GST and DTD in lung and forestomach, and SOD and CAT in kidney. Thus, besides liver, other organs viz., lung, kidney and forestomach were also stimulated by Adhatoda, to increase the potential of the machinery associated with the detoxification of xenobiotic compounds. But, liver and lung showed a more consistent induction. Since the study of induction of the phase I and phase II enzymes is considered to be a reliable marker for evaluating the chemopreventive efficacy of a particular compound, these findings are suggestive of the possible chemopreventive role played by Adhatoda leaf extract.
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PMID:Modulatory influence of Adhatoda vesica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism, antioxidant status and lipid peroxidation in mice. 1112 64


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