Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-acetylpenicillamine, 5 mmol/kg body weight increased biliary excretion of methyl mercury more than three fold. Upon simultaneous administration of the same dose of N-acetylpenicillamine and 2,5 mmol/kg body weight of S-methylcysteine biliary excretion of methyl mercury increased only 1.5 fold. In both cases biliary sulfhydryl concentration increased to the same extent, about 5 fold. Decreased biliary excretion of methyl mercury, as a result of liver depletion of reduced glutathione by cyclohexene oxide, could be restored by N-acetylpenicillamine. This restoration could be depressed by S-methylcysteine. The experiments undertaken indicate that N-acetylpenicillamine potentiated methyl mercury excretion occurs by a glutathione S-transferase dependent mechanism. Bile, collected after successive administration of methyl mercuric chloride, cyclohexene oxide, S-methylcysteine and N-acetylpenicillamine contained the methyl mercuric derivatives of N-acetylpenicillamine and glutathione together with other methyl mercury carrying components not present in control bile. Whether these components play any role in the mechanism of N-acetylpenicillamine potentiated methyl mercury excretion cannot be stated from the present investigation.
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PMID:N-acetylpenicillamine potentiated excretion of methyl mercury in rat bile: influence of S-methylcysteine. 649 13

The S-methylated derivatives of N-acetylpenicillamine, thiola and cysteine as well as methyl iodide decreased biliary excretion of methyl mercury markedly. Excretion of sulfhydryl in bile was not influenced by S-methyl-cysteine, S-methylthiola, S-methyl-N-acetylpenicillamine or a low dose of methyliodide (0.5 mmol/kg body weight). This seems to indicate that coupling of methyl mercury to glutathione in the liver before biliary excretion is a glutathione S-transferase dependent reaction. It also indicates that the methylthiols tested, or metabolites of these compounds are likely to be inhibitors of S-transferase. The effect of S-methylcysteine and low doses of methyl iodide probably reflects glutathione S-transferase inhibition as both compounds are metabolized to the S-transferase inhibitor S-methylglutathione in the liver. A higher dose of methyl iodide (1 mmol/kg body weight) seems to deplete the liver of reduced glutathione through S-methylation as illustrated by decreased biliary excretion of sulfhydryl. S-methylthiola and S-methyl-N-acetylpenicillamine are metabolized in the liver to unknown components which are excreted in bile. Whether S-methylthiola and S-methyl-N-acetylpenicillamine are inhibitors of S-transferase themselves or cause inhibition through metabolites cannot be stated from the present investigation.
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PMID:The mechanism of biliary excretion of methyl mercury: studies with methylthiols. 662 83

S-Methylcysteine (SMC) occurs in a variety of plants, including Allium sativum, Phaseolus vulgaris, and Cruciferae. In this study, we synthesized five organosulfur compounds (OSCs), SMC and four analogs, and examined their modifying effects on diethylnitrosamine-induced neoplasia of the liver in male F344 rats, using the medium-term bioassay system of Ito (Ito test) based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular focl. All OSCs examined had a tendency to decrease the number of GST-P-positive foci when given in the promotion stage of the Ito test, and in particular SMC and cysteine exerted significant inhibitory effects. When given during the initiation stage, these two OSCs also significantly inhibited focus formation. Regarding the mechanism underlying the inhibitory effects of SMC and cysteine, measurement of ornithine decarboxylase in SMC- and cysteine-treated liver tissues after partial hepatectomy (PH) revealed a significantly reduced activity, and the proportion of hepatocytes positive for proliferating cell nuclear antigen was significantly decreased by SMC or cysteine administration. Moreover, examination of the expression of the early response proto-oncogenes, c-fos, c-jun, and c-myc, after PH demonstrated down-regulated induction of c-jun mRNA transcripts by SMC, sustained for an eight-hour period. Our results support the view that SMC and cysteine are chemopreventive agents for rat hepatocarcinogenesis and that their intake may be importance for cancer prevention.
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PMID:S-methylcysteine and cysteine are inhibitors of induction of glutathione S-transferase placental form-positive foci during initiation and promotion phases of rat hepatocarcinogenesis. 924 99

Environmental compounds are known to be involved in both the generation and prevention of many human cancers. It is important to discover naturally occurring or synthetic compounds which can block the process of carcinogenesis. We have focused attention on several organosulfur compounds (OSCs) in garlic and onion, and analyzed their potential for chemoprevention in the post-initiation stage in a liver medium-term bioassay (Ito test) and a multi-organ carcinogenesis bioassay. In the ITO test, rats were given diethylnitrosamine (DEN), 200 mg/kg b.w., i.p.; starting 2 weeks later they were treated with test chemicals for 6 weeks and then killed. All rats were subjected to 2/3 hepatectomy 1 week after the start of test chemical treatment. Inhibitory effects of a number of compounds could be identified in terms of reduced numbers and areas of liver glutathione S-transferase placental (GST-P) positive foci. In the multi-organ carcinogenesis bioassay, rats were given DEN, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N'-dimethylhydrazine, and dihydroxy-dipropylnitrosamine during the first 4 weeks, followed by test chemicals for 24 weeks. Various organs were examined. As a result, oil-soluble OSCs such as methyl propyl disulfide and propylene sulfide demonstrated inhibitory effects on the development of GST-P positive foci. Moreover, water-soluble OSCs such as S-methylcysteine and cysteine similarly decreased GST-P focus formation. In contrast, OSCs such as diallyl sulfide, diallyl trisulfide, and allyl methyl trisulfide enhanced formation of such altered hepatocellular foci. Inhibitory potential for colon and renal carcinogenesis was observed in rats treated with diallyl disulfide. Thus, the results indicate that some OSCs exert chemopreventive effects on chemical carcinogenesis. It must, however, be borne in mind that they may also demonstrate promotion potential, depending on the organ examined.
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PMID:Cancer prevention by organosulfur compounds from garlic and onion. 959 Nov 99

The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis in a medium-term bioassay previously developed by Ito were examined. Initiation was induced by a single dose of diethylnitrosamine (DEN), followed by dietary administration of the promoter sodium phenobarbital (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the animals at week 3. Inhibitory potential was evaluated by analyzing two markers of carcinogenesis, namely numbers of glutathione S-transferase placental form (GST-P)-positive foci, and proliferating cell nuclear antigen (PCNA). In addition, the level of ornithine decarboxylase (ODC), one of the rate-limiting enzymes of polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced significant reduction in the areas of GST-P-positive foci. A significant reduction in the PCNA index was observed in the entire liver as well as in GST-P-positive areas. SMC also induced down-regulation of the ODC enzyme activity. Thus, SMC and cysteine were found to inhibit the promotion stage of DEN-induced hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.
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PMID:Inhibitory effects of S-methylcysteine and cysteine on the promoting potential of sodium phenobarbital on rat liver carcinogenesis. 1096 17

The aim of the present study was to examine the chemopreventive efficacy of S-methylcysteine (SMC) on rat hepatocarcinogenesis induced by concurrent administration of sodium nitrite (NaNO(2)) and morpholine (Mor) using a medium-term rat liver carcinogenesis bioassay (Ito test). Administration of SMC caused significant reduction in the areas of glutathione S-transferase placental form positive foci along with a significant decrease of hepatocyte 5-bromo-2'-deoxyuridine (BrdU) labeling indices. These results demonstrated potent chemopreventive effects of SMC against hepatocarcinogenesis due to concurrent administration of Mor and NaNO(2). SMC could thus be an effective chemopreventive agent for decreasing the risk of carcinogenicity from environmental precursors of N-nitroso compounds.
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PMID:Chemopreventive effects of S-methylcysteine on rat hepatocarcinogenesis induced by concurrent administration of sodium nitrite and morpholine. 1107 18

The chemopreventive effects of five water-soluble organosulfur compounds, S-methylcysteine (SMC) and four analogs, were examined on the promotion stage of diethylnitrosamine hepatocarcinogenesis in male F344 rats, using the medium-term bioassay (Ito test), which is based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of a putative neoplastic lesion, glutathione S-transferase placental form (GST-P)--positive hepatocellular foci. SMC and cysteine significantly decreased the number and area of GST-P--positive foci when given in the promotion stage of the Ito test. When given during the initiation stage, these two organosulfur compounds also significantly inhibited focus formation. Liver ornithine decarboxylase activity after two thirds partial hepatectomy and the proportion of hepatocytes positive for proliferating cell nuclear antigen significantly decreased the number of aberrant crypt foci in the colon in a multiorgan carcinogenesis bioassay of rats. These results support SMC and cysteine as chemopreventive agents for hepatocarcinogenesis and colon carcinogenesis. Their intake may be of importance for cancer.
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PMID:Suppression of chemical carcinogenesis by water-soluble organosulfur compounds. 1123 14

N-acetylcysteine (NAC) and S-methylcysteine (SMC), water soluble organosulfur compounds contained in garlic, were evaluated for chemoprevention of hepatocarcinogenesis after 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) initiation in rats. Intergastric treatment with NAC or SMC five times a week resulted in decreased numbers and areas of preneoplastic, glutathione S-transferase placental form (GST-P) positive foci of the liver in a dose-dependent manner. Moreover, cell proliferation was reduced in GST-P positive foci by NAC and SMC. Insulin-like growth factor I (IGF-I) and inducible nitric oxide synthase (iNOS) mRNA expressions were found downregulated in the liver by NAC. The studies indicate that NAC can serve as a chemopreventive agent for rat hepatocarcinogenesis induced by MeIQx by reducing cell proliferation, which may involve IGF-I and iNOS downregulation.
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PMID:N-acetylcysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage. 1633 51