Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen-derived free radicals might play a role in the injury produced by reperfusion of ischemic organs. Since the generation of reactive oxygen species results in an increased formation of glutathione disulfide, we have attempted to document an oxidant stress during reperfusion of ischemic liver by following the hepatic production of glutathione disulfide in vivo and in the perfused rat liver. Following partial hepatic ischemia of 120 min duration, the plasma concentration of glutathione disulfide gradually increased from 0.8 +/- 0.1 to 9.1 +/- 1.6 microM (mean +/- S.E., n = 6) after 1 hr of reperfusion. The plasma concentration of reduced glutathione increased only 2-fold from 21.4 +/- 2.4 to 38.1 +/- 3.4 microM. The rise in plasma glutathione disulfide was higher with increasing duration of ischemia from 30 to 120 min and was associated with a gradual increase in hepatic glutathione disulfide. The hepatic origin of glutathione disulfide was documented in the perfused rat liver where the release of glutathione disulfide increased gradually during reperfusion following 90 min of warm ischemia from 1.0 +/- 0.1 to 2.6 +/- 0.5 nmole per min per gm liver at 30 min after onset of reperfusion. The administration of allopurinol, an inhibitor of xanthine oxidase, did not decrease the release of glutathione disulfide (29.9 +/- 3.8 nmoles per gm in controls vs. 44.7 +/- 10.0 nmoles per gm in 30 min with allopurinol) and ALT (3.3 +/- 1.4 units per gm in controls vs. 2.6 +/- 0.8 units per gm in 30 min with allopurinol). Our studies document an oxidant stress associated with reperfusion of ischemic liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant stress during reperfusion of ischemic liver: no evidence for a role of xanthine oxidase. 337 74

Ethanol at initial concentrations between 0.75 and 6 g/l produced a dose-dependent release of the enzymes glutamic-pyruvic-transaminase and sorbitol dehydrogenase (GPT, SDH) from the isolated perfused rat liver. At the concentration of 6 g/l, it also decreased the oxygen consumption and elevated the calcium content of the isolated livers. These toxic effects of ethanol were significantly enhanced in livers, the glutathione content of which had been depleted by pretreatment with phorone. Ethanol-induced toxicity in glutathione-depleted isolated livers could be prevented both by inhibition of alcohol dehydrogenase with 4-methylpyrazole and of xanthine oxidase with allopurinol. In rats, in vivo, 1.6 g/kg ethanol injected intravenously produced a small increase in serum GPT and SDH concentrations 4 h after its administration. This increase in enzyme activities was several-fold higher and longer lasting in rats pretreated with phorone. Glutathione depletion per se did not induce hepatotoxicity in vitro or in vivo. Since glutathione is involved in several lines of defense against oxidative damage, our results of an enhanced susceptibility of glutathione-depleted livers to ethanol toxicity favour the hypothesis that ethanol exerts its hepatotoxic action via an activation of molecular oxygen.
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PMID:Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo. 360 86

Crocetin is a major component in the fruit of Gardenia jaminoides Ellis, a Chinese herbal medicine. Its protective action and mechanism against oxidative damage were investigated and mechanism against oxidative damage were investigated. Reactive oxygen species (ROS) were generated enzymatically in the xanthine-xanthine oxidase (X/XO 5 microM/0.01 u/ml) system and non-enzymatically in the paraquat (PQ 5 mM) system. Both systems increased leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT) in rat primary hepatocytes, but the hepatotoxicity was significantly suppressed on pretreatment with crocetin (10, 20 microM). Crocetin decreased formation of malondialdehyde (MDA) as an index of lipid peroxidation induced by ROS. The oxyradical generation by X/XO or PQ caused DNA damage evaluated with unscheduled DNA synthesis (UDS) in rat primary hepatocytes. The addition of crocetin decreased genotoxicity evaluated with UDS in both systems. The data showed that crocetin also inhibited the formation of superoxide anion in the X/XO system and bleached the free radical 1, 1-diphenyl-2- picrylhydrazyl (DPPH). The protective action of crocetin operated via quenching of the superoxide anion and/or free radical.
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PMID:Crocetin protects against oxidative damage in rat primary hepatocytes. 758 79

Xanthine oxidase may contribute to oxygen free radical formation during reoxygenation after hypoxia, but in humans the enzyme is present in substantial amounts only in the liver and intestine. We developed a sensitive assay for xanthine oxidase using 14C-xanthine as substrate and investigated whether xanthine oxidase was released into the systemic circulation when 19 newborn pigs were resuscitated after severe hypoxemia. In five piglets plasma xanthine oxidase concentrations increased from undetectable levels to a median value of 8 (range 4-18) microU/ml after 30 min of reoxygenation. In these pigs serum aspartate aminotransferase increased from 45 to 148 U/l, while alanine aminotransferase was unchanged (28-31 U/l). The release of xanthine oxidase did not seem to correlate with the severity of the histological brain damage after 4 days. We conclude that only low levels of xanthine oxidase are released to the systemic circulation after severe hypoxemia in newborn pigs.
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PMID:Release of xanthine oxidase to the systemic circulation during resuscitation from severe hypoxemia in newborn pigs. 763 44

An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg-1) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg-1, which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No documentable role for xanthine oxidase in the pathogenesis of hepatic in vivo ischaemia/reperfusion injury. 786 19

1. A series of flavonoids isolated from Indian medicinal plants: kaempferol-3-O-galactoside, hispidulin, nepetin, scutellarein, scutellarein-7-O-glucuronide, hibifolin and morelloflavone were studied for their activity as inhibitors of microsomal lipid peroxidation and scavengers of oxygen free radicals in vitro as well as in a model of xenobiotic toxicity in mouse. 2. All compounds inhibited lipid peroxidation in vitro. The most potent compounds were nepetin (non-enzymic lipid peroxidation) and morelloflavone (enzymic lipid peroxidation) with IC50's in the micromolar range. Some of the compounds behaved as scavengers of hydroxyl radical in the deoxyribose degradation assay, with a calculated rate constant for kaempferol-3-O-galactoside of 1.55 x 10(10) M-1 s-1. 3. Scutellarein and nepetin were found to be inhibitors of xanthine oxidase activity, whereas morelloflavone acted as a scavenger of superoxide generated by hypoxanthine/xanthine oxidase. 4. Treatment of mice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactoside after bromobenzene intoxication decreased serum glumate-pyruvate transaminase activity, although only the last flavonoid was able to significantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased bromobenzene toxicity.
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PMID:Influence of a series of natural flavonoids on free radical generating systems and oxidative stress. 797 32

The acute administration of ethanol by gastric catheter significantly increases the plasma xanthine oxidase activity in both rats and hamsters without changing other enzyme activities--alanine aminotransferase and aspartate aminotransferase. The plasma xanthine oxidase level seems to be a sensitive marker of liver damage. Its higher activity due to the acute ethanol intoxication may have an impact on ethanol organ damage.
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PMID:Plasma xanthine oxidase level and alcohol administration. 814 77

Reactive oxygen metabolites generated from xanthine oxidase play an important role in the pathogenesis of ischemia-induced tissue injury. In a hemorrhagic shock model of ischemia-reperfusion, the intracellular enzyme xanthine oxidase was released into the vasculature. This intravascular source of superoxide (O2.-) and hydrogen peroxide (H2O2) interacted reversibly with glycosaminoglycans of vascular endothelium and markedly concentrated xanthine oxidase at cell surfaces, enhancing its ability to produce extensive damage to remote tissues. Rats were made hypotensive by hemorrhage, maintained for 2h, and reinfused with shed blood. Blood samples were obtained prior to hemorrhage and 15, 30, 60, and 90 min after reperfusion for determination of xanthine oxidase (XO), lactate dehydrogenase (LDH), and alanine transaminase (AST). These enzymes were not significantly elevated in control animals. Reperfusion after hemorrhage-induced ischemia resulted in significantly elevated AST and LDH in both low heparin (100 U/h) and high heparin (1000 U/h) groups. Xanthine oxidase was detected in the circulation only after 90 min reperfusion in the low heparin group and was elevated during the entire reperfusion period in the high heparin group. Studies with cultured vascular endothelium showed significant heparin-reversible binding of XO to cellular glycosaminoglycans. These results suggest that XO can gain access to the circulation following ischemia, where it then binds to the vascular endothelial cells to produce site-specific oxidant injury to organs remote from the site of XO release.
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PMID:Xanthine oxidase activity in the circulation of rats following hemorrhagic shock. 822 22

It has been reported that vasodilatory prostaglandins have cytoprotective effects against various types of liver damage. We investigated the effects OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. Intraperitoneal administration of OP 2507 at 1,500 micrograms/kg lessened both an increase in serum alanine aminotransferase activity and an inhibition of starvation ketosis, both of which were induced by carbon tetrachloride. At lower doses, however, OP 2507 not only failed to ameliorate the carbon tetrachloride-induced changes, but it actually exaggerated them. Although the deterioration of carbon tetrachloride-induced liver damage by lower doses of OP 2507 was not statistically significant, it seems possible that OP 2507 has dual effects on carbon tetrachloride-induced liver damage. While none of the three agents cimetidine, reduced glutathione and deferoxamine, prevented increase in serum alanine aminotransferase activity induced with lower dose OP 2507, allopurinol had a tendency to prevent the increase, indicating that lower doses of OP 2507 may promote a reaction catalyzed by xanthine oxidase. We propose that both the co-administration of prostaglandins and other potentially hepatotoxic drugs, and the administration of prostaglandins to patients with drug-induced liver damage should be done carefully.
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PMID:Effects of OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. 872 10

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.
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PMID:The protective effect of allopurinol on cholestatic liver injury induced by bile duct ligation. 884 6


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