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 disposition of bromosulfophthalein was studied in chronically bile duct obstructed rats. In this model a catheter was inserted into the common bile duct and the distal tip was sealed. Resumption of bile flow was achieved with great ease. Obstruction of bile duct for 18 days in rats resulted in elevated bilirubin, ALT, AST, and alkaline phosphatase levels. Portal hypertension developed within this period (11.6 +/- 0.5 in obstructed rats vs. 8.6 +/- 0.6 mm Hg in sham-operated group). After the bile duct obstruction was opened, the half-life time for elimination of bromosulfophthalein (42.30 +/- 6.47 min) was longer than in sham-operated rats (21.23 +/- 3.34 min). Plasma clearance was reduced by 70% in bile duct obstructed rats. In spite of increased bile flow rate, biliary excretion of the dye was reduced by 40% in chronically bile duct obstructed rats. Hepatic glutathione levels were significantly reduced by 20% in this model. The specific activity of glutathione S-transferase with chlorodinitrobenzene and styrene oxide, as substrates, was reduced by 50% and 30%, respectively. However, the percent of conjugated bromosulfophthalein in bile was similar to that of sham-operated rats.
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PMID:Bromosulfophthalein disposition in chronically bile duct obstructed rats. 150 59

To assess the effect of prolonged administration of midazolam or isoflurane on hepatocellular integrity, we measured the concentrations of glutathione transferase (EC 2.5.1.18) B1 subunit and the activities of alanine aminotransferase (ALT; EC 2.6.1.2) and aspartate aminotransferase (AST; EC 2.6.1.1) in 40 patients who required long-term sedation with low-dose midazolam or isoflurane. Blood samples were collected before and 24 h after the start of the sedation and 0, 24, 72, 120, and 172 h after the last dose. ALT and AST activities did not change appreciably, but the glutathione transferase B1 concentration decreased significantly (P less than 0.03) at all times studied. The patients who received isoflurane and those who received midazolam showed no significant differences in any of the enzyme tests. We conclude that long-term sedation with midazolam or isoflurane is unlikely to affect hepatocellular integrity.
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PMID:Aspartate aminotransferase, alanine aminotransferase, and glutathione transferase in plasma during and after sedation by low-dose isoflurane or midazolam. 156 9

In the companion paper we demonstrated that hepatic vitamin E in rats becomes depleted and extrahepatic pools of vitamin E are altered by treatment with 1,2-dibromoethane (DBE). Vitamin E depletion may be dependent upon initial steps of DBE metabolism that are either oxidative (cytochrome P450 dependent) or conjugative (glutathione transferase dependent). That the liver content of glutathione (GSH) and vitamin E, the plasma concentration of vitamin E, and the serum activities of AST and ALT may be influenced by cytosolic metabolism of DBE was assessed by comparison of findings from rats treated with either 1,2-dichloroethane (DCE) or 1-bromo-2-chloroethane (BCE). The extent of oxidative metabolism was diminished by the use of tetradeutero-DBE (d4-DBE), and the availability of GSH for conjugative metabolism was diminished by pretreatment of rats with L-buthionine-S,R-sulfoximine (BSO) prior to treatment with DBE. Our results indicate that neither DCE nor BCE provokes a liver vitamin E depletion in rats, that d4-DBE treatment hastens but does not enhance the observed hepatic vitamin E depletion by comparison to animals treated with an equimolar dose of DBE, and that BSO pretreatment prevented the hepatic vitamin E depletion observed from animals treated with DBE alone. These results indicate that hepatic vitamin E depletion is the unique sequelae to conjugation of GSH with DBE, and we suggest the reactive episulfonium ion intermediate or a macromolecular adduct of this ion derived from DBE may play a role in liver vitamin E depletion associated with exposure to DBE.
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PMID:Modification of hepatic vitamin E stores in vivo. III. Vitamin E depletion by 1,2-dibromoethane may be related to initial conjugation with glutathione. 189 41

The rabbit hemorrhagic disease virus (RHDV) (isolate AST/89) RNA-dependent RNA-polymerase (3Dpol) coding region was expressed in Escherichia coli by using a glutathione S-transferase-based vector, which allowed milligram purification of a homogeneous enzyme with an expected molecular mass of about 58 kDa. The recombinant polypeptide exhibited rifampin- and actinomycin D-resistant, poly(A)-dependent poly(U) polymerase. The enzyme also showed RNA polymerase activity in in vitro reactions with synthetic RHDV subgenomic RNA in the presence or absence of an oligo(U) primer. Template-size products were synthesized in the oligo(U)-primed reactions, whereas in the absence of added primer, RNA products up to twice the length of the template were made. The double-length RNA products were double stranded and hybridized to both positive- and negative-sense probes.
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PMID:Expression of enzymatically active rabbit hemorrhagic disease virus RNA-dependent RNA polymerase in Escherichia coli. 952 22

The aim of this study was to compare the possible role of normothermic recirculation with the role of liver transplants from non-heart-beating donor pigs after 20 min of cardiac arrest. Three groups were studied, of which two were control groups: group 1, in which the liver was harvested from a heart-beating donor; group 2, in which the liver was harvested after a period of cardiac arrest followed by total body cooling; and group 3, in which the liver was procured as in group 2, but including a period of 30 min of cardiopulmonary bypass and tissue oxygenation at 37 degrees C before total body cooling. Survival at 5 days; endothelial (hyaluronic acid) and hepatocellular damage (AST, ALT, and alpha-GST); adenine nucleotides (energy charge), and histological changes were evaluated. Normothermic recirculation during 30 min showed a significant effect on survival (p = .03), endothelial damage (p < .05), and histological changes after reperfusion (p = .04). Cardiopulmonary bypass significantly increased the energy charge during the normothermic recirculation period (p = .001). Moreover, this study shows that a significant survival (100%) can be achieved with a liver allograft after 20 min of cardiac arrest. Although the liver suffers a major insult in terms of endothelial damage and hepatocellular damage, lesions caused by the ischemic injury are reversible. Histological changes also indicate lesion reversibility, since they almost disappear after 5 days.
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PMID:Liver conditioning after cardiac arrest: the use of normothermic recirculation in an experimental animal model. 987 Feb 71

The study aimed to evaluate the behavior of alpha-glutathione S-transferase (alpha-GST) in the serum of hemodialysis patients with hepatitis C virus (HCV) infection following treatment with high-dose IFN-alpha-2b. Ten patients with detected anti-HCV antibodies and HCV RNA by RT-PCR were selected and treated with high-dose interferon (IFN)-alpha-2b, 10 million units s.c. daily for 2 weeks followed by 3 times per week for 6 additional weeks. Blood samples were obtained from these patients at baseline for plasma alpha-GST and hepatic aminotransferases. Patients were monitored with weekly blood counts and monthly liver enzymes. Biochemical (normal alpha-GST and ALT) and virologic (negative HCV RNA by RT-PCR) responses were observed in 3 (30%) of the 10 patients. At the end of the follow-up (follow-up duration 44 weeks), 3 patients demonstrated long-term biological and virologic responses and 7 had relapses. In the nonresponders plasma AST and ALT approached normal levels on some occasions despite persistent viral RNA. In contrast to transaminases alpha-GST remained distinctly elevated in nonresponders and provided a more clear distinction between the responders and nonresponders. In conclusion, plasma alpha-GST, as a sensitive and reliable marker of response, may have a role in the monitoring of hemodialyzed patients undergoing IFN-alpha-2b therapy.
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PMID:The role of alpha-glutathione S-transferase in the monitoring of hemodialysis patients with hepatitis C virus infection undergoing high-dose interferon-alpha-2b therapy. 1022 80

In order to explore the effect of Panax vietnamensis on carbon tetrachloride-induced hepatotoxicity, mice were pretreated for 7 days with either crude extract or total saponins. Crude extract and total saponins dramatically decreased carbon tetrachloride-induced increase of serum GST alpha level (-50.0%, -49.5% respectively). Serum AST level was significantly decreased only with total saponins (-52.2%) and ALT level was slightly modified. In vitro experiments shown that both preparations at high concentrations (> 2000 micrograms/ml) are able to inhibit CYP2E1 enzymatic activity in mouse and human microsomes. However, we did not observe any modification of Cyp2e1 gene expression (enzymatic activity, protein and mRNA levels) in mice treated with either crude extract or total saponins. Taken together, these data demonstrated that Panax vietnamensis could be used as an hepatoprotectant. However, the mechanism of action is not associated with CYP2E1 expression, as previously suggested in vitro in rat for total saponins from Panax ginseng.
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PMID:Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression. 1119 27

The virus genome-linked protein (VPg) coding region from rabbit hemorrhagic disease virus (RHDV) (isolate AST/89) was expressed in Escherichia coli by using a glutathione S-transferase-based vector. The recombinant polypeptide could be purified in good yields and was uridylylated in vitro from [alpha-32P]UTP in a reaction catalyzed by the recombinant RNA-dependent RNA polymerase from RHDV in the absence of added template RNA. The use of deletion and point mutants allowed the identification of Tyr-21 as the residue involved in uridylylation and consequently in the linkage between VPg and the viral genome. These data constitute the first report on the identity of the amino acid residue involved in VPg uridylylation in a member of the Caliciviridae family.
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PMID:Identification of the amino acid residue involved in rabbit hemorrhagic disease virus VPg uridylylation. 1136 64

Recent studies have reported on the toxicity and related oxidative stress of selenium and mercury. The present study compares the effects of Se as sodium selenite (Na2SeO3) and Hg as mercuric chloride (HgCl2) separately and in combination. Rats received repeated oral doses of Se (0.5 micromol/ml), Hg (0.5 micromol/ml), or Se in combination with Hg (0.5 micromol/ml of each) for 5 consecutive days. Rat serum, brain and liver samples were collected for biochemical assays. The following biochemical alterations occurred in response to Hg treatment: protein content (brain and liver), acetylcholinesterase (AChE) (brain and serum), acid and alkaline (AcP and AlP) phosphatases (plasma and liver) and glutathione S-transferase (GST) (plasma and liver) activities were significantly (P<0.05) decreased, while lactate dehydrogenase (LDH) (plasma, brain and liver), aspartate and alanine aminotransferase (AST, ALT) (serum and liver) activities were significantly increased. Thiobarbituric acid reactive substances (TBARS) was significantly increased in brain and liver. Effect of Se alone included decreased AcP, AlP and GST (serum and liver) activities. However, LDH (serum, brain and liver) and AST (liver) and TBARS (brain and liver) increased. Selenium in combination with Hg partially or totally alleviated the toxic effects of Hg on different studied enzymes. It is concluded that Se could be able to antagonize the toxic effects of mercury.
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PMID:Effects of selenium and mercury on the enzymatic activities and lipid peroxidation in brain, liver, and blood of rats. 1149 25

Laparoscopic surgery causes a reduction in hepatic blood flow due to a number of factors, including raised intra-abdominal pressure, the neurohumoral response to surgical stress and the effect of patient position. The clinical significance of the phenomenon is not fully understood. Plasma concentrations of alcohol dehydrogenase (AD) and glutathione S-transferase (GST), which are concentrated in the centrilobular acinus of the liver, sensitively reflect hepatic hypoperfusion, and can be used to monitor reductions in hepatic blood flow. We compared perioperative AD, GST, aspartate aminotransferase (AST, normal range 14-32 IU litre(-1)) and alanine aminotransferase (ALT, normal range 8-41 U litre(-1)) concentrations in patients undergoing laparoscopic cholecystectomy or laparoscopic colectomy to study how patient position and surgical manipulation of the liver affect hepatocellular integrity during laparoscopy. There were significant postoperative increases in AD and GST in the cholecystectomy group [mean (SD) peak concentration 10.8 (4.7) U litre(-1) and 113 (55) microg litre(-1) respectively]. Although the duration of pneumoperitoneum was longer in the colectomy group, there were no comparable perioperative increases in AD and GST in this group [peak concentration 4.0 (4.0) U litre(-1) and 33 (35) microg litre(-1) respectively]. AST and ALT on the first postoperative day were significantly higher in the laparoscopic cholecystectomy group (41 and 34 U litre(-1) respectively) than in the laparoscopic colectomy group (24 and 18 U litre(-1); P<0.05 for each). These results indicate that patient position and the effects of surgical manipulation of the liver affect perioperative hepatic perfusion significantly.
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PMID:Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy. 1187 31


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