Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00031 (Glutathione)
 5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the administration of tryptophan and/or cysteine on carbon tetrachloride (CCl4)-induced hepatic injury were investigated. Rats received CCl4 (1 ml/kg ip) followed 6 hr later by tryptophan (300 mg/kg) and/or cysteine (950 mg/kg) via stomach tube and rats were killed after 24 hr. Treatment with tryptophan, cysteine, or both reduced the degree of hepatic necrosis observed histologically. While CCl4 caused polyribosomal disaggregation and decreased [14C]leucine incorporation into liver proteins in vitro and in vivo, treatment with tryptophan, cysteine, or both caused a shift in polyribosomes toward heavier aggregation and protein synthesis was increased. Serum activities of lactic dehydrogenase (LDH), glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl-transpeptidase were markedly increased after CCl4 alone but after subsequent treatment with cysteine or with tryptophan and cysteine appreciable decreases occurred. Glutathione concentration decreased but total amount remained constant in the livers of CCl4-treated rats while subsequent treatment with cysteine alone or together with tryptophan elevated both levels of glutathione. Using isolated hepatocytes, CCl4 caused decreases in cell viability, in release of LDH, and in [14C]leucine incorporation into protein. Treatment with CCl4 and tryptophan and/or cysteine revealed that cysteine alone or with tryptophan improved cell viability and decreased LDH release of the cells, while tryptophan alone or with cysteine improved protein synthesis. Upon cytologic evaluation, the isolated hepatocytes revealed membrane distortions after CCl4 alone but these were less marked after CCl4 plus tryptophan, cysteine, or both (most improvement). Thus, tryptophan and cysteine act in a beneficial manner against CCl4-induced hepatic injury in the rat.
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PMID:Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury. 406 14

Glutathione is important in cellular defense against oxidative stress. We postulated that administration of N-acetylcysteine (NAC), a glutathione precursor, might help maintain or replenish hepatic glutathione stores, thereby reducing reperfusion injury in liver grafts after warm ischemia. Eighteen pigs were subjected to 2 hr of warm hepatic ischemia and divided into a control group (group A, n = 6), a preischemia treatment group (group B, n = 6: NAC, 150 mg/kg, continuous i.v. infusion 1 hr before ischemia), and a postischemia treatment group (group C, n = 6: NAC, 150 mg/kg continuous i.v., begun 20 min before reperfusion and continued for 1 hr). At initiation of laparotomy, we measured hepatic levels of reduced glutathione (GSH), its oxidized form (GSSG), ATP, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Before reperfusion, after 2 hr of warm ischemia, GSH, GSSG, and ATP were measured. One hour after reperfusion, we measured GSH, GSSG, ATP, AST, and LDH. Bile output was recorded every 10 min. Postoperfusion AST and LDH were significantly lower in both treatment groups than in controls. In group B, hepatic glutathione was maintained at significantly higher levels than in controls, even after ischemia (P < 0.05). In group C, although hepatic GSH levels fell until reperfusion, after administration of NAC, hepatic GSH reached the level of the preischemia treatment group. In both treatment groups, GSH 1 hr after reperfusion was significantly higher than in the controls (P < 0.01): regeneration of glutathione was seen in all 6 animals in group C, compared with 2/6 in group B and none in the control group. ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.
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PMID:N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. 856 May 64

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 micromol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P<0.05) and liver (**P<0.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P<0.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.
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PMID:Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. 1060 94

The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects.
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PMID:Effect of black tea on lipid peroxide and glutathione levels in female rats. 1120 8

Prolonged low-medium intensity exercise is associated with increased oxidative stress in humans. We hypothesized that competitive equine endurance racing would induce changes in circulatory antioxidants and produce systemic oxidative stress. Forty horses competing in a 140-km endurance race in warm conditions [shade temperature 15-19 degrees C; 62-88% relative humidity (%RH)] were sampled before (Pre), immediately after exercise (End) and at approximately 16 h into recovery (+16 h). Plasma ascorbic acid concentration was not different between Pre [11.1 (median); 4.6-20.3 micromol/L (range)] and End [9.7; 3.0-38.9 (range) micromol/L] but was significantly decreased at +16 h (5.5; 2.8-15.5 micromol/L; P < 0.05). Total red cell hemolysate glutathione (TGSH) concentration was significantly reduced by exercise (Pre 1261; 883-1532 micromol/L; End 1065; 757-1334 micromol/L; P < 0.05) and at +16 h recovery (1032; 752-1362 micromol/L; P < 0.05). Glutathione redox ratio was unchanged by exercise but was significantly decreased at +16 h compared with that at both Pre and End (P < 0.05). The concentration of total barbituric acid reactive substances (TBARS) in plasma was increased compared with that at Pre (309; 66-1048 nmol/L), both at End (408; 170-1196 nmol/L; P < 0.05) and +16 h (380; 99-1161 nmol/L; P < 0.05). alpha-Tocopherol was unchanged by exercise or recovery. Mean race speed was 16.5 +/- 1.6 km/h and ranged from 13.9 to 19.7 km/h. Mean speed during competition in horses that completed the full 140 km (n = 28) was significantly correlated with end of exercise ascorbic acid (r = 0.622; P = 0.0004). Although there were increases in creatine phosphokinase (CK), aspartate aminotransferase (AST) and TBARS and a loss of TGSH, this study failed to demonstrate evidence of classical oxidative stress.
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PMID:Changes in circulatory antioxidant status in horses during prolonged exercise. 1204 74

The objective of this study was to investigate the effect of ascorbic acid (AA) on the in vitro cytotoxicity of cypermethrin (CM), and on glutathione (GSH) metabolism in rat hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage were measured, as indicators of hepatic damage, at 1, 15 and 30 min of exposure to CM. Glutathione and the activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (gamma-GT) were also measured. CM hepatotoxicity increased in a time and dose-dependent manner. In the presence of 30 microM CM, ALT and AST also increased 49 and 130% (P < 0.05), respectively, indicating metabolic hepatocyte damage. AA (1 mM) was capable to preserve 100% of cell integrity and modulated ALT and AST. Furthermore, CM induced a 27% reduction in the endogenous antioxidant GSH, and increased 203% GST and 283% gamma-GT (P < 0.05), indicating an oxidative insult. The presence of AA showed chemopreventive capacity against CM, recovering 60% of GSH and a 54% decrease in gamma-GT activity. These results suggest that AA in a 1:33 (CM:AA) ratio can modulate up to 90% of the damage caused to the cells by CM. It also demonstrates that AA can act as a primary antioxidant and hepatoprotector in rat hepatocytes.
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PMID:Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes. 1463 57

Glutathione-S-transferases and glutathione play a key role in the detoxification of most toxic agents. In the present study, the protective effects, if any, of isoflavone phytoestrogens--genistein and daidzein on the carbon tetrachloride (CCl4) induced changes in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S transferase (GSH) and levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)-were studied. The activities of ALT and AST were assayed in the serum, whereas the activity of GST and levels of GSH and TBARS were determined in the livers of rats. The current study involved the division of animals into two main groups: (i) rats pretreated with genistein and daidzein for three days; and (ii) non-pretreated rats. In the pretreated group, rats received oral doses of genistein (7.9 micromol/kg body weight) and daidzein (7.9 micromol/kg body weight) for three consecutive days (once daily) followed by oral dose of CCl4 on the 4th and the 5th day concurrently with the phytoestrogens-genistein or daidzein. In the non-pretreated group animals received oral dose of CCl4 (1 ml/kg body weight) for two consecutive days along with the phytoestrogens-genistein or daidzein. Treatment of male rats with CCl4 significantly elevated the activity of ALT and AST in serum and levels of TBARS in the liver. On the other hand, CCl4 resulted in decreased activity of GST and lowered the GSH levels. Coadministration of genistein and daidzein with CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to normal control levels. However, repeated dose treatments with genistein and daidzein for three days prior to the administration of CCl4 restored such alterations to normal levels. Our results indicate that genistein is more effective than daidzein in counteracting the inhibition of GST activity caused by CCl4 and restoring it to normal levels. Genistein was also more effective than daidzein restoring the induced TBARS levels caused by CCl4 to normal control levels when rats were pretreated with the isoflavone orally for three days. It has been observed that the tested isoflavonoids were able to antagonize the toxic effects of CCl4. Such counteracting effects were more pronounced for genistein and when the phytoestrogens were administered as repeated doses prior CCl4 administration.
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PMID:Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the livers of male Wistar rats. 1596 80

The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-propyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electrospray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.
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PMID:Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male ICR mice. 1627 76

The aim of the present study was to investigate the anti-schistosomal activity of colostral and mature camel milk on Schistosoma mansoni infected mice. Six weeks post infection, mean percentage of protection was detected through the hepatic portal vein. Glutathione-s-transferase (GST), alanine, aspartate transaminase (ALT and AST) and immunoglobulin G (IgG) levels were detected in sera of treated mice before and after infection. Antischistosomal activity of colostral and mature camel milk on Schistosoma mansoni infected mice were 12.81% and 31.60% respectively. The results showed that GST levels in sera of mice fed on colostral and mature camel milk were increased with mean values of 0.070, 0.108, 0.128 and 0.120 in colostral milk groups and 0. 072, 0.085, 0.166 and 0.20 in mature camel milk groups compared with the mice fed on basal diet with means values of 0.070, 0.085, 0.078 and 0.069 before infection and after two, four and six weeks of infection, respectively. On the other hand, there were slight differences on ALT and AST activities. Mice treated with colostral and mature milk (200 microl/day) showed an immunostimulatory effect by inducing IgG titers against soluble worm antigen preparation (SWAP) compared with control. Nevertheless, the difference was not considered significant (0.31 +/- 0.1) for colostrum (0.34 +/- 0.1) and for mature milk, as compared to normal control (0.2 +/- 0.04). Two, four and six weeks post infection, IgG level showed no significant change in sera from mice treated with colostral and mature milk as compared to control. In conclusion, colostral and mature camel milk showed an immuno-modualatory effect in normal healthy mice by inducing IgG and GST levels before and after infection with Schistosoma mansoni. Colostral and mature camel milk have a protective response against schistosomiasis.
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PMID:Anti-schistosomal activity of colostral and mature camel milk on Schistosoma mansoni infected mice. 1632 52

To identify the hepatoprotective component from the leaves of Cirsium setidens (Compositae), the methanolic extract was divided into two fractions, chloroform and butanol fractions, and their hepatoprotective efficacy was evaluated in a rat model of hepatic injury caused by D-galactosamine (GalN). Hepatoprotective activity was measured by the activity of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Glutathione metabolism was measured via biochemical parameters such as glutathione (GSH), glutathione reductase (GR), gamma-glutamylcysteine synthetase (GCS), glutathione S-transferase (GST), and superoxide dismutase (SOD) levels. We subjected the butanol fraction, which had higher activity, to column chromatography to yield pectolinarin, which was further hydrolyzed to yield pectolinarigenin. Administration (10, 20 mg/kg, p.o.) of the main flavonoid glycoside component, pectolinarin, and its aglycone, pectolinarigenin, for 2 weeks significantly decreased the activity levels of AST, ALT, ALP and LDH, indicating that the two compounds have hepatoprotective activity. Pectolinarin and pectolinarigenin also increased activity levels of GSH, GR, GCS, and GST, as well as SOD. The significant effect was only seen in SOD activity. This suggests that the two components exhibit hepatoprotective activity mainly via SOD antioxidant mechanism.
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PMID:Pectolinarin and Pectolinarigenin of Cirsium setidens Prevent the Hepatic Injury in Rats Caused by D-Galactosamine via an Antioxidant Mechanism. 1837 79


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