Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxin-producing cyanobacteria pose a world-wide health threat to humans and animals due to their increasing presence in both drinking and recreational waters. The predominant cyanotoxin, microcystin-LR (MCLR), targets the liver and its toxicity depends on the uptake and removal rates in the liver. The role of the glutathione detoxification pathway in protecting the liver from the effects of MCLR was investigated. Mice exposed to a single 75% LD(50) dose of pure MCLR were sacrificed at 8, 16, 24 and 32 h post-exposure (pe). Toxin induced liver damage was observed 8 and 16 h pe as evidenced by raised serum ALT and LDH levels, reduced glycogen levels and liver histology. A significant increase in lipid peroxidation was seen at 16 h pe that decreased after 24 and 32 h pe, the time-points which showed significant increases in GPX activity. An increase in soluble GST activity was noted between 8 and 16 h pe, levels of total GSH increased at 24 h while oxidised glutathione increased throughout the investigation. The increase in activity of both GPX and GST corresponded with increased transcription of these enzymes, as well as the rate-limiting enzyme in GSH synthesis, gamma-glutamyl transferase. In conclusion, this study confirms that an increase in GST activity is critical for the detoxification of MCLR, that this is regulated at the transcriptional level, and that exposure to MCLR induces the de novo synthesis of GSH. Finally, we report the involvement of GPX in the removal of MCLR-induced lipid hydroperoxides.
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PMID:An investigation into the detoxification of microcystin-LR by the glutathione pathway in Balb/c mice. 1500 45

The GBV-C/HGV (HGV) virus was discovered a few years ago. This virus is known to be parenterally as well as sexually transmitted. However, no study has found some pathogenic roles for HGV so far. In the present study, we aimed to investigate the transmission of HGV by blood components transfused to 284 patients hospitalized in surgery unit in 1995. We tested two parameters of infection in blood components transfused to infected recipients: viral RNA by PCR and anti-E2 antibodies by ELISA. We tried to suspect some potent hepatocyte impacts by assessing the levels of two enzymes in serums: alanine aminotransferase (ALT) and alpha-glutathion S-transferase (alpha-GST). We found that HGV-RNA was detectable in 3.6% of recipients prior to transfusion and 7.5% post-transfusion. For each infected recipient, we retrospectively did a search for HGV-RNA in each transfused blood component, and we found at least one blood component as HGV-RNA-positive for each transfusional infected recipient. Anti-E2 antibody prevalence standing for a former and cured infection was 39.6% in all the recipients. In viremic recipients, ALT levels were mostly normal, while alpha-GST levels were found more commonly elevated than in non-viremic recipients although non-significantly (20% vs. 6.3%; P = 0.07). The present study underlines that HGV transmission is mostly transfusional in surgery units, and that infectiosity of blood components can be anticipated by detection of the viral RNA by PCR. Furthermore, the possible relationship between the serum activity of alpha-GST and the hepatotropism of HGV, although non-admitted as pathogenic, should be investigated.
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PMID:[Hepatitis G virus and labile blood products: role of transfusional transmission]. 1512 Jan 3

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin. In this study the cardio protective effect of Centella asiatica on myocardial marker enzymes and antioxidant enzymes in adriamycin induced cardiomyopathy was investigated in rats. The rats administered with adriamycin (2.5 mg/kg body wt, i.p) caused myocardial damage that was manifested by the elevation of serum marker (LDH, CPK, GOT and GPT) enzymes and showed significant changes in the antioxidant enzymes (SOD, CAT, GPx, GST). Pre-co-treatment with Centella asiatica(200 mg/kg of body wt/oral) extract significantly prevented these alterations and restored the enzyme activities to near normal levels. These findings demonstrate the cardio protective effect of Centella asiatica on antioxidant tissue defense system during adriamycin induced cardiac damage in rats.
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PMID:Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. 1555 70

Using our ELISA kit for GST-alpha, we tested the serum GST-alpha levels of patients with hepatitis A, acute hepatitis B (HB), chronic active HB, chronic persistent HB and liver cirrhosis. Serum GST-alpha levels in all these groups of patients were significantly higher than those in the controls (P < 0.01). Serum GST-alpha levels was closely (P < 0.01) correlated with serum alanine transaminase (ALT) levels in various groups of patients except chronic persistant HB. The combined application of the two markers, GST-alpha and ALT, raised the sensitivity of detection for liver diseases. In detection of chronic persistent HB patients, the GST-alpha marker was more sensitive than ALT (P < 0.01). The follow-up data of GST-alpha and ALT markers in serum showed that the GST-alpha level could reflect the clinical progression of liver disease more exactly as observed in 79 liver cancer patients in then GST-alpha and ALT positive rate were 81% and 61% respectively (P < 0.01). In 30 persons with positive HBsAg, the positive rates of GST-alpha and ALT were 70% and 37%, respectively. These results indicated that, (1) the detection of GST-alpha combined with ALT was capable of increasing the sensitivity for recognizing hepatocellular damage; (2) the elevation of serum GST-alpha level mainly resulted from the increased expression of GST-alpha in liver cells during hepatocarcinogenesis, thus, the GST-alpha is thought to be a tumor marker for liver cancer; (3) GST-alpha measurement offers advantage over ALT for the detection of minor degree of hepatocellular damages. GST-alpha may act as an early, sensitive and specific enzyme marker.
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PMID:[Studies on the relationship between purified alpha class glutathione S-transferase (GST-alpha) and hepatocellular damage]. 1561 36

Organ dysfunction following liver resection is one of the major postoperative complications of liver surgery. The Pringle maneuver is often applied during liver resection to minimize bleeding, which in turn complicates the postoperative course owing to liver ischemia and reperfusion. Routinely, hepatocellular damage is diagnosed by, for example, abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the prothrombin time (PT). The cytosolic liver enzyme alpha-glutathione S-transferase (alpha-GST) has recently been shown to have good sensitivity for detecting hepatic injury after acetaminophen poisoning or liver transplantation, but its role in non-transplantation liver surgery has not been assessed. In this prospective randomized clinical study, the diagnostic role of plasma alpha-GST following warm ischemia and reperfusion is reported. A total of 75 patients who underwent liver resection were randomly assigned to three groups: (1) without Pringle (NPR); (2) with Pringle (PR); (3) with ischemic preconditioning by 10 minutes of ischemia and reperfusion each prior to the Pringle manuever (IPC). The major findings are as follows: (1) ALT, AST, and alpha-GST increased upon liver manipulation as early as prior to resection, with a rapid return of alpha-GST values to preoperative levels, whereas ALT and AST further increased on the first postoperative day. (2) In the PR group, alpha-GST, but not ALT and AST, was significantly elevated compared with that in the NPR group at 15 and 30 minutes and 2 hours after resection/reperfusion. In addition, only levels of alpha-GST significantly correlated with the Pringle duration. (3) The ischemia/reperfusion-induced early rise in alpha-GST was completely prevented by ischemic preconditioning. Moreover, only alpha-GST concentrations (> 490 microg L(-1)) determined early after resection (2 hours) predicted postoperative liver dysfunction (24 hours PT < 60%) with a positive predictive value of 74% and a negative predictive value of 76%. Thus alpha-GST seems to be a sensitive, predictive marker of ischemia/reperfusion-induced hepatocellular injury and postoperative liver dysfunction.
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PMID:Alpha-gluthathione S-transferase as an early marker of hepatic ischemia/reperfusion injury after liver resection. 1577 1

For experimental machine perfusion (MP) of the liver, the modified University of Wisconsin solution (UW-G) is most often used. In our search for an enriched MP preservation solution, Polysol was developed. Polysol is enriched with various amino acids, vitamins, and other nutrients for the liver metabolism. The aim of this study was to compare Polysol with UW-G for MP preservation of the liver. Rat livers were preserved during 24 hours with hypothermic MP using UW-G (n = 5) or Polysol (n = 5). Hepatocellular damage (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], alpha-glutathione-S-transferase [alpha-GST]) and bile production were measured during 60 minutes of reperfusion (37 degrees C) with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours of cold storage in UW (n = 5). MP using UW-G or Polysol showed less liver damage when compared with controls. Livers machine perfused with Polysol showed less enzyme release when compared to UW-G. Bile production was higher after MP using either UW-G or Polysol compared with controls. In conclusion, machine perfusion using Polysol results in better quality liver preservation than cold storage with UW and machine perfusion using UW-G.
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PMID:Improved rat liver preservation by hypothermic continuous machine perfusion using polysol, a new, enriched preservation solution. 1583 88

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

Microcystins are usually the predominant cyanotoxins present in both drinking and recreational waters after cyanobacterial blooms. Their classic toxic effect is hepatotoxicity through inhibition of serine/threonine phosphatases. However, recent studies also reported oxidative stress generation and disruption of ion regulation in aquatic organisms after microcystins exposure. In the present study, aqueous extracts of Microcystis aeruginosa were administered to the estuarine crab Chasmagnathus granulatus (Decapoda, Brachyura) by gavage in variable doses (from 34 to 860 microg kg(-1)) and exposure times (6, 12, and 72 h). A control group was exposed to saline solution. Analyzed variables included oxygen consumption, lipid peroxidation (LPO), enzyme activities (glutathione S-transferases or GST; alanine aminotransferase or ALT; aspartate aminotransferase or AST; and lactate dehydrogenase or LDH), glycogen, and microcystins content. Oxygen consumption increased in organisms exposed for 12h to 860 microg kg(-1) of microcystins and a similar result was observed after 72 h at doses equal to or higher than 34 microg kg(-1). LPO levels increased in doses equal to or higher than 34 microg kg(-1) after 72 h. GST and LDH activities increased after 12 h (at a dose of 860 microg kg(-1)), but ALT and AST activities remained unaltered in all experimental conditions. Glycogen content decreased after 72 h exposure at doses equal to or higher than 172 microg kg(-1). After 12h of exposure to 860 microg kg(-1) of microcystins, the concentration found in the hepatopancreas of C. granulatus was 13.17+/-0.56 microg kg(-1). In crabs exposed to doses higher than 172 microg kg(-1) during 72 h this value raised to 32.14+/-4.12 microg kg(-1). The obtained results indicated that microcystins exposure led the tissue to an oxidative stress condition (high LPO levels), at least in part favored by the augment of oxygen consumption, altering the glycogen metabolism. GST responses were only observed in the short-term experiment (12 h) and no effect on classical markers of vertebrate liver damage (ALT and AST) was observed. Although the hepatopancreas from C. granulatus accumulated a relatively low concentration of toxins, it was enough to induce physiological and biochemical disturbances.
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PMID:Biochemical and physiological responses after exposure to microcystins in the crab Chasmagnathus granulatus (Decapoda, Brachyura). 1613 63

The aim of this work was to investigate the protective role of baker's yeast Saccharomyces cerevisiae against the hepatotoxic effect of the drug flutamide that is widely used for treatment of metastatic prostate adenocarcinoma. Administration of flutamide to adult male rats in a dose of 100 mg/kg b.w. daily for 15 days resulted in serious hepatic injury. Highly significant increase in each of serum ALT, ALP, bilirubin, bile acids and cholesterol level, relative to the control group, was observed. Also, a highly significant increase in the serum glutathione-S-transferase isoforms: alpha-GST and pi-GST and each of TNF-alpha and NO levels was recorded. Moreover, highly significant decrease in hepatic glutathione peroxidase and superoxide dismutase activities was observed. In addition, the authors noticed a significant increase in serum testosterone levels with concomitant highly significant increase in serum acid phosphatase activity. Prophylactic treatment of male rats with baker's yeast in a dose of 4.8 mg/kg b.w. daily for 15 days, followed by a combination of flutamide (100 mg/kg b.w.) and yeast (4.8 mg/kg b.w.) daily for other 15 days resulted in marked improvement in rat's liver function, whereas the serum testosterone and acid phosphatase levels retained values parallel to those recorded for the flutamide-treated rats. Histological examination of liver tissues showed that flutamide caused hydropic degeneration, necrotic areas and marked increase in Kupffer cells. The central vein is congested with blood and signs of apoptosis appeared in the hepatocytes in the form of fragmentation of the nuclei and blebbing of the cytoplasm. On the other hand, in the rats treated with both yeast and flutamide, the hepatic cords were more regularly arranged, signs of degeneration or apoptosis were less pronounced and some hepatocytes appeared binucleated. The authors postulate that each one of the powerful antioxidative components in S. cerevisiae effectively participated in attenuation of the oxidative stress caused by flutamide metabolites, and in promoting regeneration of new hepatocytes and meanwhile could restore liver function beyond normal status.
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PMID:Saccharomyces cerevisiae intervention for relieving flutamide-induced hepatotoxicity in male rats. 1622 70

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.
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PMID:Synergistic interactions of ferulic acid with ascorbic acid: its cardioprotective role during isoproterenol induced myocardial infarction in rats. 1644 96


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