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)

Tripterygium glycosides (TG), extracted from the Chinese herb Tripterygium wilfordii Hook. f, is a widely used anti-inflammatory and immunosuppressive agent with definite nephrotoxicity. However, its toxic mechanism remained undiscovered. The aim of this study was to characterize the potential toxicity of TG on segments of proximal tubule in rats. Six hundred and 1200 mg/kg of TG was administered by daily intragastric instillation for 16 days. A significant reduction of p-aminohippurate accumulation by renal cortical slices indicated that TG damaged organic anion transporter (OAT) system that localized at the proximal tubule, especially S(2) segment. A dramatic loss of kidney glutamine synthetase (GS) activity induced by TG reflected S(3) segment damage. Because mRNA expression of OAT1, OAT3, and GS was decreased substantially, we ascribe the fall of p-aminohippurate accumulation and GS activity to alterations at the transcriptional level. A dose-related diminution of kidney glutathione S-transferase activity was noted simultaneously, suggesting oxidative stress involvement. Histopathological lesions were observed in the TG intoxicated rat kidney even though there were no obvious changes of serum urea and creatinine at this dose level. In summary, we provided evidences supporting that TG caused segment-specific dysfunction in the kidney proximal tubule.
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PMID:Segment-specific proximal tubule injury in tripterygium glycosides intoxicated rats. 1911 Oct 4

Although an association between diet, especially cruciferous vegetables, and colorectal cancer has been hypothesized, recent studies have been inconsistent with their findings. One possibility for the discrepant results is that the interaction with related genes has not generally been considered. The present study examined the associations among urinary isothiocyanates, glutathione S-transferase (GST) polymorphisms, and colorectal cancer risk in a case-control study nested within the Multiethnic Cohort Study, based in Hawaii and Los Angeles, California. We measured prediagnositic urinary isothiocyanate levels adjusted for creatinine and analyzed GSTM1, GSTT1, and GSTP1 polymorphisms in 173 cases and 313 matched controls, with biospecimens collected between 2001 and 2006. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals (95% CI). A detectable amount of urinary isothiocyanates was associated with a 41% decrease in colorectal cancer risk (95% CI, 0.36-0.98). No significant, main-effect associations were seen with a homozygous deletion of the GSTM1 or GSTT1 polymorphism, or with the AG or GG genotypes for GSTP1 rs1695. There was a weak suggestion that for individuals with the GSTP1 AG or GG genotype, a detectable amount of isothiocyanates further decreases one's risk of colorectal cancer compared with those with the GSTP1 AA genotype, but the interaction term was not statistically significant (P = 0.09). This is only the second study published on the association between urinary isothiocyanates and colorectal cancer risk. The results suggest that further studies, with larger numbers, examining a possible interaction with the GSTP1 polymorphisms are warranted.
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PMID:Urinary isothiocyanates; glutathione S-transferase M1, T1, and P1 polymorphisms; and risk of colorectal cancer: the Multiethnic Cohort Study. 1912 14

As a result of the widespread use of Cd in industry and its extensive dissemination in the environment, there has been considerable interest in the identification of early biomarkers of Cd-induced kidney injury. Kim-1 is a transmembrane glycoprotein that is not detectable in normal kidney, but is up-regulated and shed into the urine following ischemic or nephrotoxic injury. Recent studies utilizing a sub-chronic model of Cd exposure in the rat have shown that Kim-1 is an early urinary marker of Cd-induced kidney injury. Kim-1 was detected in the urine 4-5 weeks before the onset of proteinuria and 1-3 weeks before the appearance of urinary metallothionein and Clara cell protein 16, which are standard markers of Cd nephrotoxicity. In the present study, we have compared the time course for the appearance of Kim-1 in the urine with the time course for the appearance of alpha glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucose amidase (NAG) and Cd, each of which have been used or proposed as urinary markers of Cd nephrotoxicity. Adult male Sprague-Dawley rats were given daily subcutaneous injections of 0.6 mg (5.36 micromoles)/kg Cd, 5 days per week for up to 12 weeks. One day each week, 24 h urine samples were collected and analyzed for protein, creatinine and the various markers. The results showed that significant levels of Kim-1 appeared in the urine as early as 6 weeks into the treatment protocol and then continued to rise for the remainder of the 12 week treatment period. By contrast, significant levels of alpha-GST and NAG did not appear in the urine until 8 and 12 weeks, respectively, while proteinuria was not evident until 10 weeks. The urinary excretion of Cd was below the level of detection until week 4 and then showed a slow, linear increase over the next 6 weeks before increasing markedly between weeks 10 and 12. These results provide additional evidence that Kim-1 is a sensitive biomarker of the early stages of Cd-induced proximal tubule injury.
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PMID:Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity. 1937 16

The effect of combined therapy with diphenyl diselenide (PhSe)(2) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) against alterations induced by mercury (Hg(2+)) was evaluated. Mice were exposed to mercuric chloride (HgCl(2)) (1mg/kg, subcutaneously) for two weeks. After that, mice received (PhSe)(2) (15.6 mg/kg), or DMPS (12.6 mg/kg), or a combination of both for one week. Thiobarbituric acid-reactive substances (TBARS), ascorbic acid and Hg(2+) levels and glutathione S-transferase (GST) and catalase (CAT) activities were carried out in kidney. Hematological parameters, plasmatic bilirubin, uric acid, urea and creatinine levels as well as lactate dehydrogenase (LDH) activity were determined. (PhSe)(2) or DMPS restored the increase in LDH activity and TBARS, bilirubin, uric acid, urea and creatinine levels caused by HgCl(2). The levels of erythrocytes, hemoglobin and hematocrit reduced by HgCl(2) exposure were restored by (PhSe)(2) or DMPS administration in mice. Leukocyte and platelet counts modified by HgCl(2) exposure were restored by (PhSe)(2) or DMPS therapy. DMPS restored the increase in Hg(2+) levels induced by exposure to HgCl(2). Concomitant administration of (PhSe)(2) and DMPS reduced the effectiveness of DMPS in restoring damage induced by HgCl(2). Combined therapy with (PhSe)(2) and DMPS was less effective than isolated therapies in restoring the damage induced by HgCl(2) in mice.
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PMID:Concomitant administration of sodium 2,3-dimercapto-1-propanesulphonate (DMPS) and diphenyl diselenide reduces effectiveness of DMPS in restoring damage induced by mercuric chloride in mice. 2097 24

Aluminium is present in many manufactured foods and medicines and is also added to drinking water during purification purposes. Therefore, the present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of aluminium chloride (AlCl3) on biochemical parameters, antioxidant enzymes and lipid peroxidation of male Wistar Albino rats. Animals were assigned to 1 of 4 groups: control; 34 mg AlCl3/kg bw; 50 mg propolis/kg bw; AlCl3 (34 mg/kg bw) plus propolis (50 mg/kg bw), respectively. Rats were orally administered their respective doses daily for 70 days. The levels of thiobarbituric acid reactive substances (TBARS) was increased, and the activities of glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were decreased in liver, kidney and brain of rats treated with AlCl3. While, TBARS was decreased and the antioxidant enzymes were increased in rats treated with propolis alone. Plasma transaminases, lactate dehydrogenase, glucose, urea, creatinine, bilirubin, total lipid, cholesterol, triglyceride and LDL-c were increased, while total protein, albumin and high HDL-c were decreased due to AlCl3 administration. The presence of propolis with AlCl3 alleviated its toxic effects in rats treated with AlCl3. It can be concluded that propolis has beneficial influences and could be able to antagonize AlCl3 toxicity.
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PMID:Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats. 1942 29

Cisplatin is one of the most potent chemotherapeutic antitumor drugs. Oxidative stress has been proven to be involved in cisplatin-induced toxicity. Therefore, the present study was undertaken to examine the antioxidant potential of grape seed proanthocyanidin extract (GSPE) against the toxicity of cisplatin in male rats. Cisplatin treated animals revealed a significant elevation in plasma, heart, kidney and liver thiobarbituric acid reactive substances (TBARS), while the activities of antioxidant enzymes (GST, SOD, CAT and GSH-Px, and the levels of glutathione (GSH) were decreased. Aspartate and alanine transaminases (AST and ALT), creatine kinase and lactate dehydrogenase were significantly increased in plasma, while liver AST and ALT were significantly decreased. Cisplatin significantly increased the levels of plasma total lipid, cholesterol, urea and creatinine, and the relative weight of kidney. On the other hand, plasma total protein and albumin, and body weight were significantly decreased. GSPE reduced cisplatin-induced the levels of TBARS in plasma, heart, kidney and liver, TL, cholesterol, urea and creatinine, and liver AST and ALT. Moreover, it ameliorated cisplatin-induced decrease in the activities of antioxidant enzymes, and GSH, total protein and albumin. Therefore, the present results revealed that GSPE exerts a protective effect by antagonizing cisplatin toxicity.
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PMID:Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. 1942 35

In this study we evaluated the effect of diphenyl diselenide (PhSe)(2) on glycerol-induced acute renal failure in rats. Rats were pre-treated by gavage every day with (PhSe)(2 )(7.14 mg kg(-1)) for 7 days. On the eighth day, rats received an intramuscular injection of glycerol (8 mL kg(-1)). Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities and ascorbic acid levels were evaluated in renal homogenates. Histopathological evaluations were also performed. The results demonstrated that (PhSe)(2) was able to protect against the increase in urea and creatinine levels and histological alterations in kidney induced by glycerol. (PhSe)(2) protected against the inhibition in delta-ALA-D, CAT and GPx activities and the reduction in ascorbic acid levels induced by glycerol in kidneys of rats. In conclusion, the present results indicate that (PhSe)(2) was effective in protecting against acute renal failure induced by glycerol.
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PMID:Diphenyl diselenide protects against glycerol-induced renal damage in rats. 1948 1

The aim of this study was to investigate the possible protective role of the dietary flavonoid quercetin on cadmium (Cd)-induced nephrotoxicity using biochemical and histopathological approaches. In experimental rats oral administration of CdCl(2) (5mg/kg) for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid and creatinine with a significant (p<0.05) decrease in creatinine clearance. Cd also significantly (p<0.05) decreased the levels of urea, uric acid and creatinine in urine. Cd-induced oxidative stress in kidney tissue was indicated by the increased levels of renal lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl content with a significant (p<0.05) decrease in non-enzymatic (total sulphydryl group, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD)). Moreover the kidneys of Cd-treated rats showed tubular necrosis, degeneration, dilation, desquamation, thickening of basement membrane and luminal cast formation. Quercetin treatment markedly attenuated the Cd-induced biochemical alterations in serum, urine and renal tissue. Quercetin also ameliorated the Cd-induced pathological changes when compared with Cd-alone-treated group. These data indicate that the natural dietary antioxidant quercetin might have protective effect against Cd-induced nephrotoxicity and oxidative stress in rats.
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PMID:Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats. 1961 71

Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidence suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Aulosira fertilisima Ghose (EEA) was evaluated using cisplatin (5 mg/kg(-1) i.p.)-induced renal damage in rats. EEA showed higher significant effect on DPPH radical scavenging activity as compared with methanol extract of A. fertilisima (MEA) and water extract of A. fertilisima (WEA). Thus, EEA was selected for further in vivo studies. The serum urea and creatinine levels in the cisplatin alone-treated group were significantly elevated with respect to normal group of animals. The levels were reduced in the EEA (100 mg/kg, p.o) plus cisplatin-treated groups. Renal oxidative stress was determined by renal TBARS, CD and reduced glutathione levels, and by enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin-produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the study indicated that A. fertilisima significantly and dose-dependently protected the nephrotoxicity induced by cisplatin. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.
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PMID:Effects of Aulosira fertilisima against cisplatin-induced nephrotoxicity and oxidative stress in rats. 2019 85

The existence of oxidative stress and the higher incidence of cardiovascular diseases in association with uremia is well proved. The uremic status of serum copper, ceruloplasmin (CP), protein thiols, malonyldialdehyde (MDA), and glutathione S-transferase (GST) levels was studied. The study was carried out on 51 chronic renal failure (CRF) patients who were not on hemodialysis therapy and on 42 healthy controls. Serum urea, creatinine, and MDA levels were found to be significantly increased (P < 0.001), and total protein, albumin, protein thiols, and copper levels were found to be significantly decreased in CRF patients compared to normal controls (P < 0.001). Ceruloplasmin levels were decreased significantly (P < 0.05), and there was no significant change in serum GST levels in CRF patients compared to normal controls. In conclusion, the significant increase in levels of MDA, and the decrease in levels of protein thiols, CP, and copper in uremia patients when compared to controls, reconfirms the presence of stress in this patient population. In view of the changes in other markers of oxidative stress, this absence of any significant change in the activity of GST in uremia patients compared to controls, warrants further study.
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PMID:Determination of oxidative stress markers and their importance in early diagnosis of uremia-related complications. 2035 4


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