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 individual and combined effects of dietary toasted soybean meal (3.13-25%) and dietary licorice root extract (0.38-3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50-day-old rats were started on the diets. By use of newly developed high-performance liquid chromatography-based analytic methods, measurable levels of daidzein (2.67 micrograms/ml) and glycyrrhetinic acid (7.87 micrograms/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain-related changes. At all dosages, there were no significant soybean- or licorice-related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose-dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives. The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study.
...
PMID:Effect of dietary soybean and licorice on the male F344 rat: an integrated study of some parameters relevant to cancer chemoprevention. 129 95

Epidemiologic studies suggest that the consumption of cruciferous vegetables is associated with a reduced risk for several types of cancer including cancer of colon. Experimental studies indicate that dithiolthiones, naturally occurring substances in cruciferous vegetables, possess anticarcinogenic properties. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a substituted dithiolthione, has been tested for its chemopreventive activity. We studied the effect of dietary oltipraz on liver and colonic mucosal enzymes and DNA adducts to evaluate the modulating role of this agent during the early period of azoxymethane (AOM)-induced carcinogenesis. At 6 weeks of age, groups of animals were fed the AIN-76A diet containing 0 and 300 ppm oltipraz. At 8 weeks of age, all of the animals except vehicle-treated animals were administered a subcutaneous injection of AOM (15 mg/kg body wt/week for 2 weeks). Animals intended for vehicle treatment were administered normal saline subcutaneously. Fifteen hours after the second AOM injection, six animals each from control oltipraz diet groups were sacrificed and liver and colonic mucosa from each animal were used for DNA adduct analysis. Animals intended for liver and colonic mucosal glutathione S-transferase, tyrosine specific protein kinase (TPK), and ornithine decarboxylase (ODC) enzyme assays were killed 5 days after the second AOM or saline injection. The results of this study indicated that dietary oltipraz significantly increased liver (P less than 0.001) and colonic mucosal (P greater than 0.05) weights, but had no effect on body weights (P greater than 0.05). In saline-treated animals, feeding of oltipraz significantly increased the cytosolic glutathione S-transferase (P less than 0.001) and ODC (P less than 0.05) activities in the liver and colon when compared with those fed the control diet. Although our unpublished results indicate an inhibitory role of oltipraz when fed during the initiation and postinitiation phases of intestinal carcinogenesis, the increased ODC activity may indicate a possible role of oltipraz in colon tumor promotion. Additional studies are indicated to test the antitumor properties of oltipraz administered during the postinitiation phases. AOM treatment significantly increased the TPK (P less than 0.0001) and ODC (P less than 0.01) activities in the liver and colon of animals fed the control diet. Dietary oltipraz significantly suppressed the AOM-induced TPK (P less than 0.001) activities in liver and colon and ODC (P less than 0.01) activity of colon. Analysis of nucleic acid bases, O6-methylguanine, and 7-methylguanine revealed that dietary oltipraz significantly (P less than 0.05) inhibited the AOM-induced adduct species. These results suggest that dietary oltipraz enhances the colonic and liver glutathione S-transferase activity and reduced the formation of DNA adducts. In addition, dietary oltipraz modulates liver and colonic ODC and TPK activities that have been shown to play a role in tumor promotion.
...
PMID:Effect of oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] on azoxymethane-induced biochemical changes related to early colon carcinogenesis in male F344 rats. 202 Jun 72

Comparison of binding of specific antibodies to glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl transpeptidase (GT), ornithine decarboxylase (ODC) and the glutathione S-transferase B and P forms (GST-B, P) was made in putative pre-neoplastic lesions during their induction and subsequent development using the Solt-Farber model. The earliest focal hepatocellular lesions were evident as single, or small groups of GST-P-positive hepatocytes in tissue taken at partial hepatectomy 3 weeks after initial application of diethylnitrosamine (DEN). With the onset of proliferation and increase in size the majority of the lesions expressed elevated levels of all of the enzyme proteins investigated with a correlation between strength of binding and morphology being apparent. While [3H]thymidine incorporation was limited during the period of acetylaminofluorene administration, to the hepatocytes demonstrating altered enzyme phenotype no direct link between proliferation rate within individual foci and level of G6PD expression could be discerned. Similarly, the elevated level of labelling characteristic of persisting nodular lesions at later stages also did not correlate with degree of G6PD alteration in individual cells. The results indicate that while changed enzyme phenotype appears as an ordered pattern suggestive of physiological adaptive nature, the degree of alteration is not directly related to proliferation kinetics under the rapid induction conditions characteristic of the Solt-Farber model.
...
PMID:Immunohistochemically demonstrated glucose-6-phosphate dehydrogenase, gamma-glutamyl transpeptidase, ornithine decarboxylase and glutathione S-transferase enzymes: absence of direct correlation with cell proliferation in rat liver putative pre-neoplastic lesions. 287 98

The effects of concomitant treatment with dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), diaminopropane (DAP), an inhibitor of ornithine decarboxylase or the microsomal drug detoxifying enzyme inducer butylated hydroxyanisole (BHA) during the induction phase of rat liver nodular lesion development were investigated. Clear reductions in both number and size of foci and nodules as assayed quantitatively with the aid of marker enzymes G6PD, glutathione S-transferase P form or gamma-glutamyl transpeptidase were established for treatment with either DHEA or BHA. DAP in contrast did not exert influence on the number of lesions, but brought about a significant reduction in size. The quantitative data taken together with the finding that increased labelling of tritiated thymidine occurred in extrafocal hepatocyte populations in BHA-treated animals, give direct support to the view that alteration in enzyme phenotype within putative pre-neoplastic lesions plays a central role in their generation with this short-term model. In particular, a physiological adaptive significance of G6PD elevation is suggested.
...
PMID:Influence of dehydroepiandrosterone, diaminopropane and butylated hydroxyanisole treatment during the induction phase of rat liver nodular lesions in a short-term system. 294 Nov 78

Four organosulfur compounds from garlic and onions were examined for modifying effects on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats using the medium-term bioassay system based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas per cm2 of induced glutathione S-transferase placental form-positive foci. Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and allyl mercapton (AM) exerted enhancing effects on their development, while dimethyl trisulfide also tended to increase them. To investigate possible mechanisms of the modifying influence, sequential changes in ornithine decarboxylase activity (ODC) over 24 h were measured in AM-treated liver tissue without prior DEN initiation. The activity started to increase by 4 h after AM-treatment, and reached maximum at 16 h, compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. An increase in proliferating cell nuclear antigen-positive cells followed the elevation of ODC activity. These results suggest that IAIE, DPT, and AM promote rat hepatocarcinogenesis and their promoting effect might be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus appropriate to consider not only a possible protective role of garlic and onions, but also enhancing effects.
...
PMID:Enhancing effects of organosulfur compounds from garlic and onions on hepatocarcinogenesis in rats: association with increased cell proliferation and elevated ornithine decarboxylase activity. 782 89

The rat tracheal epithelial (RTE) cell focus inhibition assay was used to identify potential chemopreventive agents. Ninety-nine agents were evaluated for their ability to inhibit benzo[a]pyrene-induced transformation of RTE cells. Freshly isolated RTE cells were exposed to benzo[a]pyrene alone or in combination with a chemopreventive agent. After 30 days in culture, transformed foci were scored and inhibition was quantitated. In these studies, foci formation was inhibited mainly by agents which modulate the initiation of carcinogenesis by altering drug-metabolizing enzymes, inhibiting the binding of benzo[a]pyrene to DNA, enhancing detoxification of activated carcinogens, or by inducing epithelial cell differentiation. Such agents include antioxidants, free radical scavengers, glutathione S-transferase enhancers, vitamins, retinoids, and sulfhydryl compounds. Agents which inhibit ornithine decarboxylase and arachidonic acid metabolism were not as effective. The RTE assay provides important data for agent selection prior to whole animal-screening assays in the development of chemoprevention drugs.
...
PMID:Evaluation of chemopreventive agents in different mechanistic classes using a rat tracheal epithelial cell culture transformation assay. 783 22

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.
...
PMID:Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. 788 21

Two organosulfur compounds, methyl propyl disulfide (MPD) and propylene sulfide (PS) from garlic and onions, were studied for their modifying effects on hepatocarcinogenesis in the F344 rats. Modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form (GST-P)-positive foci in the liver. MPD and PS significantly reduced both these parameters of GST-P-positive foci in a dose-dependent manner. To investigate possible mechanisms of inhibition, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities were measured. In MPD and PS-high dose-treated liver tissue there was a tendency for their decrease, albeit non-significant, which suggested that the inhibitory effect might have been caused by decreased cell proliferation associated with decreased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus necessary to consider various effects in assessing possible protective roles of garlic and onions.
...
PMID:Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions. 798 12

Ten organosulfur compounds from garlic and onions were studied for their modifying effects on diethylnitrosamine-induced neoplasia of liver in male F344 rats using the medium-term bioassay system of Ito based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control group given diethylnitrosamine alone. In experiments 1 and 2, high doses of diallyl sulfide, diallyl trisulfide, allyl methyl sulfide, allyl methyl trisulfide, and dipropyl sulfide had enhancing effects on focus formation. In contrast, high doses of methyl propyl disulfide and propylene sulfide significantly decreased the number of glutathione S-transferase placental form-positive foci. In the third experiment, combined treatment with the five chemicals that had enhancing activity were fed at low doses and increased the induction of glutathione S-transferase placental form-positive foci. To investigate the mechanism of the modifying effect on hepatocarcinogenesis, ornithine decarboxylase activity was measured in diallyl sulfide-, allyl methyl sulfide-, and dipropyl sulfide-treated liver tissue without prior initiation with diethylnitrosamine, and its activity was increased compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. Formation of 8-hydroxydeoxyguanosine, a DNA adduct generated by activated oxygen species, and lipid peroxidation (2-thiobarbituric acid-reacting substance production) were also not changed. These results suggest that the promoting effect could be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is appropriate to consider not only the possible protective role of garlic and onions but also their enhancing effects.
...
PMID:Enhancement by organosulfur compounds from garlic and onions of diethylnitrosamine-induced glutathione S-transferase positive foci in the rat liver. 818 74

The modifying effect of dietary protocatechuic acid (PCA) given during the initiation phase or the postinitiation phase on liver carcinogenesis induced by diethylnitrosamine (DEN) was studied in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups and fed the diets containing 500 and 1000 ppm PCA or the basal diet. At 7 weeks of age, all animals except PCA alone and control groups were given DEN at 40 ppm in the drinking water for 5 weeks to induce liver cell neoplasms. Seven days after the DEN exposure, groups of animals fed the PCA diets and continued on these diets until the end of the study. All animals were necropsied during the 37 weeks after the start of the experiment in order to determine the incidences of preneoplastic liver cell foci and neoplasms. Hepatic ornithine decarboxylase activity was also measured in all animals at the termination of the study. Dietary PCA administered at both doses during the initiation phase significantly inhibited the incidence of altered hepatocellular foci resistant for iron accumulation or those positive for glutathione S-transferase placental form and the liver cell tumor incidence and multiplicity. Similarly, the numbers of liver cell foci and neoplasms and tumor multiplicity were significantly reduced in groups fed the PCA diets at the postinitiation stage of carcinogenesis. Hepatic ornithine decarboxylase activity was reduced in DEN-treated animals fed the PCA diets compared to those given DEN alone. Although the precise mechanisms of PCA-induced inhibition of hepatocarcinogenesis remain to be elucidate, it is likely that the inhibitory effects during the initiation and postinitiation phases may be due to alteration in hepatic ornithine decarboxylase activity under the present experimental condition.
...
PMID:Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats. 850 18


1 2 3 4 5 Next >>

---