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 role of nonsteroidal anti-inflammatory drugs (NSAIDs) was studied on the antioxidant defense system and nitric oxide-derived damage in a 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Early precancerous lesions were established in the proximal and distal regions of the colon by morphological and histopathological examinations that were greatly regressed by the simultaneous treatment of the three NSAIDs, such as aspirin, celecoxib, and etoricoxib, along with the procarcinogen DMH. The intestinal brush border membrane (BBM) was isolated from the two regions and the colon-specific marker enzyme cysteine-sensitive alkaline phosphatase was assayed, which showed considerable elevation by DMH but reverted back to normal level by all the three NSAIDs. DMH also caused a higher level of lipid peroxidation as measured by malonyldialdehyde production, which was also found to be corrected by the NSAIDs, in both the region of the colonic tissue. The antioxidant activities were further established by a higher level of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase in the NSAID treatment as compared to the DMH. The nonenzyme tripeptide, glutathione content was also recovered similarly as an antioxidant defense mechanism. To elucidate whether nitric oxide (NO) also plays an important role in the pathophysiology of colon cancer, the NO and citrulline levels were measured. The results show that the NO was lowered in DMH treatment and elevated by the administration of the NSAIDs while the citrulline level could not be recovered back. The findings of the present investigation indicate the chemopreventive modalities of the NSAIDs, particularly the COX-2 inhibitors.
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PMID:Antioxidative effects of nonsteroidal anti-inflammatory drugs during the initiation stages of experimental colon carcinogenesis in rats. 1854 Aug 45

Free radicals cause cell injury, when they are generated in excess or when the antioxidant defense is impaired. Carbon tetrachloride (CCl4) is used as a model for liver injury. In this study antioxidant activity of ethanol extract of A. fertilisima (EEA) was investigated using CCl4 intoxicated rat liver as the experimental model. Oral administration of EEA at a dose of 100 mg/kg body weight, for 14 consecutive days, the rate of the production of antioxidant enzymes like super oxide dismutase, catalase, glutathione peroxidase and glutathione transferase in rats compared to the CCl4 treated group without any supporting treatment. Liver damage is detected by the measurement of the activities of serum enzymes like aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and alkaline phosphatase which were released in to the blood from damaged cells. The normalization of these enzymes levels was observed in rats treated with EEA (100 mg/kg body weight) by reducing the leakage of the above enzymes in to the blood. The findings provide a rationale for further studies on isolation of active principles and its pharmacological evaluation. Protection offered by silymarin (standard reference drug) seemed relatively greater.
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PMID:Antioxidant activity of Aulosira fertilisima on CCl4 induced hepatotoxicity in rats. 1869 72

Vanadate has been recognized as a specific and potent phosphatase inhibitor since its structure is similar to that of phosphate. In this study, we measured the inhibition of glutathione S-transferase-tagged protein tyrosine phosphatase 1B (GST-PTP1B) and alkaline phosphatase (ALP) by the insulin enhancing compounds, bis(maltolato)oxovanadium(IV) (BMOV). The results showed that the activity of GST-PTP1B was reversibly inhibited by solutions of BMOV with an IC(50) value of 0.86+/-0.02 microM. Steady state kinetic studies showed that inhibition of GST-PTP1B by BMOV was of a mixed competitive and noncompetitive type. In addition, incubation of GST-PTP1B with BMOV showed a time-dependent biphasic inactivation of the protein. On the other hand, the inhibitory behavior of BMOV on ALP activity was reversible and competitive with an IC(50) value of 32.1+/-0.6 microM. Incubation with BMOV did not show biphasic inactivation of ALP. The reversible inhibition of GST-PTP1B by BMOV is more potent than that of ALP, but solutions of BMOV inhibited both enzymes. This data support the suggestion that mechanisms for the inhibitory effects of BMOV on GST-PTP1B and ALP are very different.
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PMID:Inhibition of protein tyrosine phosphatase 1B and alkaline phosphatase by bis(maltolato)oxovanadium (IV). 1872

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to assess the possible protective roles of onion (Allium cepa Linn) and garlic (Allium sativum Linn) extracts on Cd-induced testicular damage and spermiotoxicity. The control group received double distilled water; Cd group received Cd (1.5mg/100g BW/day) orally; extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5ml and 1.0ml/100g BW/day) orally for one week and then simultaneously challenged with Cd (1.5mg/100g BW/day) for additional three weeks. Testicular tissue oxidant/antioxidant status and sperm characteristics were determined. Cd caused a marked (p<0.001) rise in testicular lipid peroxidation (LPO) and glutathione S-transferase (GST) levels whereas glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and alkaline phosphatase (ALP) levels were decreased. Cd intoxication significantly (p<0.001) decreased epididymal sperm concentration and sperm progress motility, increased percent total sperm abnormalities and live/dead count. Both extracts successfully attenuated these adverse effects of Cd. Onion extract offers a dose-dependent protection. Our study demonstrated that aqueous extracts of onion and garlic could proffer a measure of protection against Cd-induced testicular oxidative damage and spermiotoxicity by possibly reducing lipid peroxidation and increasing the antioxidant defence mechanism in rats.
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PMID:Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats. 1882 5

The hepatoprotective effect of onion and garlic extracts on cadmium (Cd)-induced oxidative damage in rats is reported. Control group received double-distilled water alone. Cd group was challenged with 3CdSO(4).8H(2)O (as Cd; 1.5 mg/kg bw per day per oral) alone, while extract-treated groups were pretreated with varied doses of onion and/or garlic extract (0.5 and 1.0 ml/100 g bw per day per oral) for a week and thereafter co-treated with Cd (1.5 mg/kg bw per day per oral) for 3 weeks. Cd caused a marked (p < 0.001) increase in the levels of lipid peroxidation and glutathione S-transferase, whereas glutathione, superoxide dismutase, and catalase levels were decreased in the liver. We also observed a decrease in hepatic activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase and a concomitant increase in the plasma activities of ALT and AST. Onion and garlic extracts significantly attenuated these adverse effects of Cd. Onion extract proffered a dose-dependent hepatoprotection. Our study showed that Cd-induced oxidative damage in rat liver is amenable to attenuation by high dose of onion and moderate dose of garlic extracts possibly via reduced lipid peroxidation and enhanced antioxidant defense system that is insufficient to prevent and protect Cd-induced hepatotoxicity.
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PMID:Hepatoprotective potentials of onion and garlic extracts on cadmium-induced oxidative damage in rats. 1908 32

The present study was undertaken to validate a battery of cytotoxicity assays performed in a multiplex format to screen pharmaceutical compounds at an early stage of drug development. Two experiments were performed on HepG2 cells and the parameters were measured in 96-well plates. Biological and technical triplicates were performed to evaluate the reproducibility of the assay. In the first experiment, HepG2 cells were exposed to tamoxifen, staurosporine, phenobarbital and triton X-100 for 2 and 24h. The following nine cytotoxicity parameters were analyzed, cell viability, lactate dehydrogenase (LDH), adenosine triphosphate (ATP), caspase-3/7, aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and alpha-glutathione-S-transferase (alpha-GST). In the second experiment, HepG2 cells were exposed to doxorubicin, t-butyl hydroperoxide, ferrous sulfate and sulfamoxole for 2 and 24h. Based on the results of the first experiment, six cytotoxicity parameters were selected for further evaluation (cell viability, ATP, LDH, caspase, AST and GLDH). ALT (activity always below detection limit), ALP (no response to drug treatment) and alpha-GST (too labor intensive and not possible to multiplex) were eliminated. The analysis of the data revealed that the reproducibility of the assays was accurate according to principal component analysis. Our data also clearly indicated that the potential of this battery of selected assays measured in a multiplex format not only made it possible to rank and select the most promising drug candidates based on their cytotoxic potential, but also to gather information that may help to understand some of the toxic events occurring in the cells.
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PMID:Selection of cytotoxicity markers for the screening of new chemical entities in a pharmaceutical context: a preliminary study using a multiplexing approach. 1911 50

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.
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PMID:Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. 1940 69

Asiatic rice borer, Chilo suppressalis (Walker) (Lepidoptera: Crambidae), is a cosmopolitan and destructive pest in rice fields of the world. This pest was reported in 1973 in Iran, and it has since spread widely in rice, Oryza sativa L., fields throughout the country. In this study, we tried to evaluate comparative toxicity of diazinon in five colonies of C. suppressalis, collected from Babol (Ba), Amol (Am) of Mazandaran Province and Rasht (Ra), Sheikhmahale (Sh), and Gourabzarmikh (Go) of Guilan Province, northern Iran. The LD50 values were compared. We also evaluated the general esterases, alkaline phosphatase (ALP), glutathione transferase (GST), and acetylcholinesterase (AChE) activities from the five populations. The LD50 values of Ra, Ba, Am, and Sh (12.64, 11.4, 7.17, and 3.71 microg/mg larva(-1)) were 13.67-, 12.33-, 7.75-, and 4.02-fold higher than Go population (0.924 microg/mg larva(-1)). Using alpha-naphthyl acetate as substrate, the general esterase activities in Ra, Ba, Am, and Sh colonies were, respectively, 1.81-, 1.68-, 1.75-, and 1.35-fold more than those in Go population. When beta-naphthyl acetate was used as the substrate, activity ratio was measured 1.98-, 2.58-, 1.25-, and 1.24-fold compared with the Go population. Glutathione transferase activities in Ra, Ba, Am, and Sh populations were 1.27-, 1.68-, 0.98-, and 1.7-fold more than those in Go, when 1-chloro-2,4-dinitrobenzene was used as the substrate. When 1,2-dichloro-4-nitro-benzene was used as the substrate, activity ratio was measured 1.14-, 1.42-, 0.56-, and 0.95-fold compared with Go population. The ALP activity demonstrated a significant difference among these populations and in Ra, Ba, Am, and Sh larvae were 3.54-, 4.62-, 3.84-, and 2.18-fold more than Go. The AChE inhibition or I50 value was 0.19, 0.22, 0.31, 0.19, and 0.26 mM in Ra, Ba, Am, Sh and Go populations, respectively. However, the results showed no significant differences in studied colonies. These biochemical characterizations of general esterases ALP, GST, and AChE were consistent with diazinon bioassay in the five populations. It is inferred from increased esterase, alkaline phosphatase and glutathione transferase, activities that might play an important role in the increasing resistance in C. suppressalis to diazinon among these five populations.
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PMID:Diazinon resistance in different selected strains of Chilo suppressalis (Lepidoptera: Crambidae) in northern Iran. 1961 Apr 37

The role of oxidative stress in the pathogenesis of alcoholic diseases in the liver is well documented. Kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, possesses a variety of biological activities, including antioxidant. Our aim was to investigate in vivo whether KV may attenuate oxidative stress in liver of Wistar albino rats following chronic ethanol administration. Thirty-six male Wistar albino rats were randomly divided into six groups. Toxicity was induced by administering 7.5% or 45% ethanol at 3 g/kg of body weight daily for 8 weeks. Rats were treated with KV at 200 mg/kg of body weight for the same duration. Treatment was by oral gavage. Integrity of liver was assessed by determining the levels of serum alanine and aspartate aminotransferases (ALT and AST, respectively) and alkaline phosphatase (ALP). The antioxidant status was monitored by determining the levels of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA), the end product of lipid peroxidation (LPO). Experimentally, chronic ethanol administration led to hepatotoxicity as evidenced by the increase in levels of serum ALT, AST, and ALP. Ethanol also enhanced the formation of MDA in the liver. Specifically, MDA was elevated by 70% and 98% in animals treated with 7.5% and 45% ethanol, respectively. Levels of hepatic SOD, CAT, GST, and GSH were significantly (P < .05) reduced by ethanol treatment. Co-administration of KV during ethanol treatment inhibited hepatic LPO and ameliorated SOD and GST activities. These findings demonstrated that KV could have a beneficial effect by inhibiting the oxidative damage in liver of Wistar rats caused by chronic ethanol administration.
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PMID:Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on ethanol-induced oxidative stress in liver of adult wistar rats. 1962 7

Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.
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PMID:Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study. 2005 64


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