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

---

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

The present paper assesses the modifying potential of black pepper on the hepatic biotransformation system in mice. The modulatory effect was assessed on glutathione S-transferase (GST), cytochrome b5 (cyt. b5), cytochrome P-450 (cyt. P-450), acid-soluble sulfhydryl (-SH) content and malondialdehyde (MDA) level. Swiss albino mice of either sex (eight weeks old) were fed on a diet containing 0.5%, 1% and 2% black pepper (w/w) for 10 and 20 days. The findings revealed a significant and dose-dependent increase in GST and -SH content in the experimental groups except the one maintained on 0.5% black pepper diet for 10 days. Elevated levels of cyt. b5 and cyt. P-450 were also statistically significant and dose-dependent. The level of MDA was lowered in the group fed on 2% black pepper diet for 20 days. Being a potential inducer of detoxication system, the possible chemopreventive role of black pepper in chemical carcinogenesis is suggested.
...
PMID:Evaluation of the modulatory influence of black pepper (Piper nigrum, L.) on the hepatic detoxication system. 840 74

Effects of acute or subchronic administration of human placental extract (HPE), a worldwide clinically used agent, on hepatic drug metabolizing enzyme activities were evaluated in rats. Hepatic microsomal cytochrome P-450 (Cyt. P450) and cytochrome b5 (Cyt. b5) contents and cytosolic glutathione S-transferase (GST) activities were maximally induced after various periods of time following a single intraperitoneal injection of HPE (4 ml/kg) whereas microsomal UDP-glucuronyltransferase (UDPGT) activities were inhibited significantly. All these altered effects were returned almost to the basal levels after 96 h of treatment. Subchronic treatment (30 days) with HPE (1,2 or 4 ml/kg) afforded a significant induction of Cyt. P-450 and Cyt. b5 levels and that of GST activities with a concurrent suppression of the activities of UDPGT and these results were found to be dose-dependent. However, microsomal NADPH cytochrome c reductase activity was not affected either by acute or subchronic treatment. The observed variations in the levels and activities of above house-keeping enzymes were discussed in relation to the possible carcinogenic risk of long-term treatment with this pharmaceutical agent.
...
PMID:Effects of human placental extract on hepatic drug metabolizing enzyme. 854 51

This paper evaluates the potential effects of arecanut (Areca catechu, L.), an important ingredient of betel quid, on the garlic (Allium sativum, L.)-modulated activities of hepatic detoxication system enzymes, acid soluble sulfhydryl content, and lipid peroxidation in mice. Mice were fed on either a normal diet or a diet containing 0.25%, 0.5%, or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment oral administration of garlic at the dose level of 20 or 100 mg/kg body weight/day was supplemented. Significant modulation in the activities of phase I and phase II enzymes, -SH content, and malondialdehyde (MDA) level by garlic was observed. Garlic-modulated alterations in glutathione S-transferase (GST) activity and -SH content were decreased, while cytochrome b5, cytochrome P-450, and MDA levels were further augmented by the arecanut plus garlic treatments.
...
PMID:Evaluation of the modifying influence of arecanut on the garlic-modulated hepatic detoxication system enzymes, sulfhydryl content, and lipid peroxidation in mice. 858 84

The modulatory influence of arecanut, a masticatory in several human populations, on the levels of biotransformation system enzymes in mouse liver has been studied. Swiss albino mice of either sex (4 weeks old) were fed on diets containing 0.25%, 0.5%, or 1% arecanut (w/w) for 5 weeks. In addition, a group of mice received a 1% arecanut diet for 36 weeks. The findings revealed a significant increase in hepatic levels of cytochrome b5, cytochrome P-450, malondialdehyde (MDA), and glutathione S-transferase (GST). The hepatic -SH content was depressed by 0.5% and 1% arecanut diets. Long-term feeding of a 1% arecanut diet elicited changes similar to those seen following treatment for 5 weeks. Arecanut-modulated profiles of biotransformation enzymes and antioxidant levels are suggestive of its influence in the process of carcinogenesis induced by bioactivated electrophilic species of potential chemical carcinogens among habitual arecanut chewers. Arecanut was also tested for its potency either to induce or to alter 7,12-dimethylbenz[a]anthracene (DMBA)-induced papillomagenesis in the skin of the mouse. Animals put on a 1% arecanut diet and treated with a standard two-stage protocol for tumor induction developed a 5.41 tumor burden (control value: 5.76) along with 100% incidence of mice bearing papillomas (control value: 94.4%), thus signifying that dietary intake of 1% arecanut for 18 weeks could not induce/alter the mouse skin tumorigenesis pattern.
...
PMID:Modulatory influence of arecanut on the mouse hepatic xenobiotic detoxication system and skin papillomagenesis. 858 85

Ellagic acid (EA), a naturally occurring plant polyphenol possesses broad chemoprotective properties. Dietary EA has been shown to reduce the incidence of N-2-fluorenylacetamide-induced hepatocarcinogenesis in rats and N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumors. In this study changes in the expression and activities of specific rat hepatic and esophageal mucosal cytochromes P450 (P450) and phase II enzymes following dietary EA treatment were investigated. Liver and esophageal mucosal microsomes and cytosol were prepared from three groups of Fisher 344 rats which were fed an AIN-76 diet containing no EA or 0.4 or 4.0 g/kg EA for 23 days. In the liver total P450 content decreased by up to 25% and P450 2E1-catalyzed p-nitrophenol hydroxylation decreased by 15%. No changes were observed in P450 1A1, 2B1 or 3A1/2 expression or activities or cytochrome b5 activity. P450 reductase activity decreased by up to 28%. Microsomal epoxide hydrolase (mEH) expression decreased by up to 85% after EA treatment, but mEH activities did not change. The hepatic phase II enzymes glutathione S-transferase (GST), NAD(P)H:quinone reductase [NAD-(P)H:QR] and UDP glucuronosyltransferase (UDPGT) activities increased by up to 26, 17 and 75% respectively. Assays for specific forms of GST indicated marked increases in the activities of isozymes 2-2 (190%), 4-4 (150%) and 5-5 (82%). In the rat esophageal mucosa only P450 1A1 could be detected by Western blot analysis and androstendione was the only P450 metabolite of testosterone detectable. However, there were no differences in the expression of P450 1A1, the formation of androstendione or NAD(P)H:QR activities between control and EA-fed rats in the esophagus. Although there was no significant decrease in overall GST activity, as measured with 1-chloro-2,4-dinitrobenzene (CDNB), there was a significant decrease in the activity of the 2-2 isozyme (66% of control). In vitro incubations showed that EA at a concentration of 100 microM inhibited P450 2E1, 1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2 activity. Using standard steady-state kinetic analyses, EA was shown to be a potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, with apparent Ki values of approximately 55 and 14 microM respectively. In conclusion, these results demonstrate that EA causes a decrease in total hepatic P450 with a significant effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities [GST, NAD-(P)H:QR and UDPGT] and decreases hepatic mEH expression. It also inhibits the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective effect of EA against various chemically induced cancers may involve decreases in the rates of metabolism of these carcinogens by phase I enzymes, due to both direct inhibition of catalytic activity and modulation of gene expression, in addition to effects on the expression of phase II enzymes, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates.
...
PMID:The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes. 862 97

The present study reports the modulatory influence of alcoholic extract from the leaves of Ocimum sanctum on the activities of cytochrome p-450, cytochrome b5, and aryl hydrocarbon hydroxylase enzymes in the liver and glutathione-S-transferase and reduced glutathione level in the liver, lung, and stomach of the mouse. Oral treatment with the leaf extract at 400 and 800 mg/kg body wt for 15 days would significantly elevate the activities of cytochrome p-450 (p < 0.05), cytochrome b5 (p < 0.01, p < 0.001), aryl hydrocarbon hydroxylase (p < 0.05), and glutathione S-transferase (p < 0.05, p < 0.01), all of which are important in the detoxification of carcinogens as well as mutagens. Moreover treatment with 400 and 800 mg/kg body wt of Ocimum extract for 15 days also significantly elevated extrahepatic glutathione-S-transferase (p < 0.05, p < 0.01). The reduced glutathione level was also elevated by treatment with the leaf extract in liver, lung, and stomach tissues (p < 0.01, p < 0.001). Mice fed a diet containing 0.75% butylated hydroxyanisole (positive control) revealed no alteration in the basal hepatic cytochrome p-450 and aryl hydrocarbon hydroxylase level, but hepatic cytochrome b5 and glutathione S-transferase activity in hepatic and extrahepatic organs were elevated in a time-responsive manner (p < 0.05, p < 0.001). The observations suggest further exploitation of the Ocimum leaf extract or its active principle(s) for the chemoprevention of chemical carcinogenesis in different animal model systems.
...
PMID:Modulatory influence of alcoholic extract of Ocimum leaves on carcinogen-metabolizing enzyme activities and reduced glutathione levels in mouse. 871 Jun 90

The effect of repeated exposures to N, N-dimethylformamide (DMF) on the liver and the hepatic microsomal monooxygenase system and glutathione metabolizing enzymes were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 1.0 ml/kg body weight (950 mg/kg), 3 times a week for 2 weeks. The gain in the body weight in the DMF group were suppressed compared with the control group at 2 week. The relative weight of the liver, spleen and kidney also appeared to increase in the DMF group as same as in the control group. Hematological examinations showed no changes. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) did not change in the DMF group. Hepatic microsomal protein and cytochrome P-450 did significantly decrease by 30% and 38%, respectively, while there was no change in cytochrome b5, NADPH-cytochrome c reductase and NADH-ferricyanide reductase. Glutathione peroxidase (GPx) activity was not affected by DMF administration, while glutathione reductase (GR) and glutathione S-transferase, (GST) activity were significantly increased by 16% and 64%, respectively. These results indicate that DMF alters tke hepatic drug metabolizing system without significant increase of the serum transaminase levels. These findings may contribute to elucidate the mechanism of DMF hepatotoxicity.
...
PMID:Alterations of hepatic drug metabolising system due to dimethylformamide (DMF). 877 55

The inducing effects of some flavonoids (flavone, flavanone, tangeretin and quercetin) and model substances have been studied in rats, and the activity and the expression of drug-metabolizing enzymes have been compared in rats. The addition of flavonoids to the diet (0.3% w/w) for 2 weeks did not change the liver cytochrome P450 content nor the activities of the NADPH-cytochrome P450 and NADH-cytochrome b5 reductases, but it affected the activities of phase I and phase II enzymes. Flavone, and to a lesser extent tangeretin, increased the activities mediated by the P450 1A1,2 (EROD) and 2B1,2 (PROD) as well as the activities of p-nitrophenol UDP-glucuronyl transferase (UGT) and glutathione transferase (GST). Flavanone mainly enhanced PROD, UGT and GST, whereas quercetin did not modify any enzyme activities. None of the tested flavonoids modulated the activities catalyzed by P450 2E1, 3A and 4A. Immunoblotting studies showed that flavone and tangeretin increased the expression of cytochrome P450 1A and 2B forms, whereas flavanone only induced cytochrome P450 2B. Flavone and to a lesser extent flavanone, markedly increased the phenol-UGT protein level. Both flavone and flavanone also increased the androsterone- and testosterone-UGTs, whereas tangeretin and quercetin did not increase any UGT isoform. We concluded that the flavonoids tested specifically affected the expression of the drug-metabolizing isozymes in rat liver, their inducing properties were dependent on their chemical structures.
...
PMID:Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver. 893 57

After 4 days of acetysal treatment (160 mg/kg body weight orally), the following were established: a higher acute toxicity of acetysal, an inducing effect on amidopyrin N-demethylase and analgin N-demethylase activity and increases in cytochrome P-450 and cytochrome b5 content. Aniline hydroxylase activity decreased, thiopental sleeping time was prolonged and UDP-glucuronyltransferase activity was not changed. Dexamethasone, at a dose of 5 mg/kg body weight p.o. for 4 days, did not change acetysal acute toxicity but at a dose of 100 mg/kg i.p. increased it. Thiopental sleeping time was shortened by dexamethasone (100 mg/kg i.p.) but was not changed by dexamethasone at 5 mg/kg p.o., alone or in combination. Dexamethasone at 5 mg/kg increased analgin N-demethylase and UDP-glucuronyltransferase activities, did not change cytochrome P-450 content and decreased aniline hydroxylase activity. The combination with 5 mg/kg dexamethasone increased the activity of amidopyrin N-demethylase, analgin N-demethylase and UDP-glucuronyltransferase and decreased those of amitriptyllin N-demethylase and aniline hydroxylase and cytochrome P-450 content. Ethylmorphine N-demethylase, benzphetamine N-demethylase, NADPH-cytochrome c reductase and glutathione S-transferase activities were not affected significantly by acetysal, dexamethasone or their combination. Hepatic carboxyl esterase was depressed by dexamethasone (5 mg/kg) and was increased by the combination. Lipid peroxidation was not changed by dexamethasone (5 mg/kg) but was decreased by acetysal and the combination.
...
PMID:Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes. 898 33

The potential of arecoline alkaloid, by direct or translactational exposure, to modify the chemopreventive efficacy of phytic acid, via modulation of hepatic biotransformation system enzymes and antioxidant defence mechanism, was assessed in a murine system. Phytic acid (500 or 1000 mg/kg b.w. per day) induced a statistically significant increase in the hepatic levels of glutathione S-transferase (GST) and sulfhydryl (-SH) in murine females and suckling neonates. The elevated levels of hepatic cytochrome b5 (Cyt. b5), cytochrome P-450 (Cyt. P-450) and the depleted level of malondialdehyde (MDA) were observed in the lactating mice. Arecoline (20 mg/kg b.w. per day) alone did not modulate the hepatic GST and -SH levels although it induced a statistically significant increase in the levels of Cyt. b5, Cyt. P-450 and MDA in the murine system. Phytic acid-modulated hepatic levels of phase II components were depressed whereas phase I enzymes and lipid peroxides were further elevated by arecoline-plus-phytic acid treatment. The implications of direct or translactational modulation in the competing potential pathways of biotransformation system enzymes in the process of chemical carcinogenesis are discussed.
...
PMID:Modulatory influence of arecoline on the phytic acid-altered hepatic biotransformation system enzymes, sulfhydryl content and lipid peroxidation in a murine system. 923 24


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---