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)

A normocalcemic animal model of vitamin D (vit. D)-deficiency has been successfully developed by feeding a high calcium (Ca2+) diet to vit. D.-deficient rats. The modulating role of Ca2+ on the hepatic antioxidant defence system and lipid peroxidation has been evaluated in this model. Partial restoration of liver function was noted in these rats following extra Ca2+ feeding. Serum alkaline phosphatase and alanine aminotransferase reverted to a normal level. The reduced levels of hepatic SOD and glutathione peroxidase in vit. D.-deficient rats, were also increased after extra Ca2+ supplementation. Even elevated lipid peroxidation due to vit. D.-deficiency was reduced after feeding the extra Ca(2+)-supplemented diet. However, catalase activity remained at the control level throughout the study. The results provide important evidence that normocalcemia is essential for maintaining the hepatic antioxidant defence and controlling lipid peroxidation in the in vivo milieu.
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PMID:The role of calcium in the modulation of the hepatic anti-oxidant defence system. 821 47

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
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PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and were incubated with different concentrations of MeHg+ (0.1-100 ppm) for 2 h. Through the incubation period the viability was determined by Trypan blue exclusion. Reduced glutathione (GSH) content and its enzymes, glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-RX) were measured. Leakage of enzymes such as aspartate transaminase (AST), and alanine transaminase (ALT) were determined. The cell viability was reduced significantly after 1 h incubation when 0.1 and 1 ppm MeHg+ were applied. The decrease in the cell viability was dose- and time-dependent. A depletion of GSH content was observed with 100 ppm MeHg+ after 30 min of incubation. A significant decrease in GSH-RX was observed with 100 ppm during 15 and 30 min of incubation, while 10 ppm of MeHg+ significantly increased ALT leakage after 60 min. However, there was a significant increase in AST leakage with 100 ppm only. The present investigation indicates that the toxic effect of MeHg+ is most likely cytosolic enzyme related.
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PMID:The mechanism of methyl mercury toxicity in isolated rat hepatocytes. 835 70

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.
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PMID:Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition. 902 73

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TBARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O2.-), since Cu-Zn superoxide dismutase activities were increased by azomethine H treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O2.-) maybe produced as a mediator of azomethine H action.
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PMID:Free radical production by azomethine H: effects on pancreatic and hepatic tissues. 916 36

The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated. After 30 days of treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome P450 system, increase in microsomal superoxide anion generation accompanied by increased levels of liver lipid peroxidation, as measured by the production of thiobarbituric acid reactants and by spontaneous visible chemiluminescence. Concomitantly, liver antioxidant defenses are slightly modified, with decreased activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase contributing to an oxidative stress condition of the liver. These liver biochemical alterations are closely related to increased levels of urinary coproporphyrin, plasma AST and ALT activities and to the onset of liver morphological lesions.
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PMID:Pro- and anti-oxidant parameters in rat liver after short-term exposure to hexachlorobenzene. 919 4

Fe(II)-tetrakis-N,N,N',N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes the dismutation of superoxide, and blocks the toxic effect of paraquat on Escherichia coli growth and survival. We examined antioxidative effects of Fe-TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates with an IC50 value of 30.2 microM, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (EC50 value is 2.6 microM). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CCl4 induced liver injuries, and improved submassive necrosis and fatty degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase activity in cytosol of rat liver. Although the exact mechanism of action is not clear, antioxidative properties as well as attenuation of hepatocellular defense systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in CCl4-intoxicated rat.
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PMID:Hepatoprotective effect of Fe-TPEN on carbon tetrachloride induced liver injury in rats. 955 61

Prevention of cellular damage after warm ischemia is of major importance in liver transplantation. In this study, we determined the extent to which lipid peroxides contribute to the pathogenesis of hepatic cell damage induced by transient warm ischemia with subsequent reperfusion. In addition, the function and immunohistochemical features of glutathione peroxidase, a potent physiological lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or 30 minutes of warm ischemia resulted in a significant elevation in serum and liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic periportal area accompanied with remarkable rises in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular damage. The adverse changes after ischemia/reperfusion were minimized by pretreatment with superoxide dismutase (SOD). These results indicate that increased lipid peroxidation by production of radicals after reperfusion caused the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase (GSH-PO) activity was significantly decreased and its location altered in the damaged liver. These findings suggest that GSH-PO contributes significantly to the protection against hepatic reperfusion injuries.
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PMID:Alterations in glutathione peroxidase activity following reperfusion injury to rat liver. 960 29

Exudative diathesis, a condition caused by a selenium (Se)/vitamin E deficiency, was studied in chicks. Trios of chicks that showed clinical signs of exudative diathesis were matched for severity. One was injected subcutaneously with 0.5 mL distilled water, and the other two received 15 microg of Se in 0.5 mL distilled water. A chick fed a diet with supplemental Se also received 0.5 mL distilled water. Blood was collected from three chicks 2 d after injection, and from the other chick, 6 d after injection. After blood was collected, pectoral muscle and bone marrow were collected. Deficient chicks showed varying degrees of necrosis in pectoral muscle, whereas recovering chicks had extensive fibrosis in pectoral muscle. An analysis of blood showed differences in CO2, glucose, Se, glutathione peroxidase, alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Heterophils and monocytes were increased in deficient chicks; lymphocytes, basophils, and hemoglobin decreased. After 6 d of recovery, all of the changes noted above were correcting toward normal. Eosinophils, in contrast, were unaffected by a deficiency, but increased in recovering chicks. It is hypothesized that cytokines associated with the inflammatory response accentuate the clinical signs of exudative diathesis.
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PMID:Changes in blood chemistry, hematology, and histology caused by a selenium/vitamin E deficiency and recovery in chicks. 963 Apr 19

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.
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PMID:Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults. 970 Nov 88


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