Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic steatosis and steatohepatitis are encountered with great frequency in people who consume large amounts of ethanol (more than 6 drinks per day). Ethanol causes steatosis by altering several steps in the hepatic processing of fatty acids, including their uptake from plasma, their use as fuel substrates, and their export as triglyceride. When clinically mild, alcoholic steatosis and steatohepatitis can be difficult to distinguish from nonalcoholic fatty liver disease. This is particularly true among individuals at high risk of accelerated alcoholic liver injury, such as women, the obese, and those with hepatitis C. In the outpatient setting, history and aspartate aminotransferase:alanine aminotransferase ratio offer the best clues to diagnosis. Liver biopsy cannot determine the cause of steatohepatitis, but can show the extent of disease. The etiology of disease is important to prognosis, as alcoholic fatty liver carries a much higher risk of progression and mortality than nonalcoholic fatty liver disease. Patients with moderate to severe alcoholic steatohepatitis are typically hospitalized. Derangements in white blood cell count, prothrombin time, and bilirubin identify those with the highest early mortality. Survival in this severely ill subgroup is improved with the short-term use of corticosteroids; patients who have contraindications to steroids may benefit from other forms of therapy, either pharmacologic, nutritional, or both.
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PMID:Alcoholic steatosis and steatohepatitis. 1194 32

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24 juvenile micropigs to receive folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury.
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PMID:Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. 1212 4

In the present study, we investigated the effect of raw as well as thermally oxidized sunflower oil (commercially available) on ethanol induced hepatotoxicity. Ethanol was given to animals at a level of 20% and sunflower oil at a level of 15%. Results show higher activity of plasma aspartate transaminase (AST) and alkaline phosphatase (ALP) and also higher levels of plasma and tissue cholesterol, phospholipids and triglycerides both in alcohol+raw as well as thermally oxidized oil groups. The level of cholesterol and triglycerides increased significantly in the liver of rats given alcohol alone, alcohol and raw as well as thermally oxidized oil but the level of phospholipids decreased. The activity of phospholipase A and phospholipase C in liver was found to be increased significantly in alcohol alone, alcohol+oil groups as compared to control group. Histopathological changes in the liver of alcohol and alcohol+oil groups were in good correlation with biochemical parameters. The liver samples of alcohol administered rats showed both microvesicular and macrovescicular type of fatty changes, where as alcohol+oil fed groups showed inflammatory cell infiltrate in the portal triad, microvesicular and macrovesicular type of fatty changes and feathery degeneration of hepatocytes. Studies on the phospholipid fatty acid composition in the liver showed the presence of a number of fatty acids in the alcohol and oil treated groups, which are not present in the control group. The results obtained thus indicate hepatotoxic and hyperlipidaemic effects of alcohol and oil given together.
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PMID:Toxic effects of sunflower oil on ethanol treated rats. 1227 Jul 41

Piper betle L. is a commonly used masticatory in Asia. This study was carried out to investigate the hepatoprotective and antioxidant properties of P. betle, using ethanol intoxication as a model of hepatotoxic and oxidative damage. Ethanol-treated rats exhibited elevation of hepatic marker enzymes and disturbances in antioxidant defense when compared with normal rats. Oral administration of P. betle extract (100, 200, or 300 mg/kg body weight) for 30 days significantly (P <.05) decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), and lipid hydroperoxides in ethanol treated rats. The extract also improved the tissue antioxidant status by increasing the levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) and the activities of free radical-detoxifying enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in liver and kidney of ethanol-treated rats. The highest dose of P. betle extract (300 mg/kg body weight) was most effective. The results were comparable with the known hepatoprotective drug, silymarin. These results indicate that P. betle could afford a significant hepatoprotective and antioxidant effect.
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PMID:Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in ethanol-treated Wistar rats. 1263 94

The study investigates the effect of aqueous extract of fenugreek seeds (Trigonella foenum graecum) on lipid peroxidation and antioxidant status in experimental ethanol toxicity in rats. The ability of the seed extract to prevent iron-induced lipid peroxidation in vitro was also investigated. Ethanol feeding for 60 days resulted in significant increases in the activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase. The levels of serum lipid hydroperoxides and thiobarbituric acid reactive substances in liver and brain were also significantly elevated. Significantly lower activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase were observed in liver and brain accompanied by depletion in glutathione, ascorbic acid and alpha-tocopherol concentrations. Activity of Ca(2+) ATPase in brain was significantly lowered. Simultaneous administration of aqueous extract of fenugreek seeds with ethanol prevented the enzymatic leakage and the rise in lipid peroxidation and enhanced the antioxidant potential. The seeds exhibited appreciable antioxidant property in vitro which was comparable with that of reduced glutathione and alpha-tocopherol. Further, histopathological examination of liver and brain revealed that, aqueous extract of fenugreek seeds could offer a significant protection against ethanol toxicity.
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PMID:Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity. 1291 70

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism, including increased levels of homocysteine and S-adenosylhomocysteine (SAH) and reduced levels of S-adenosylmethionine (SAM) and glutathione (GSH). The concept that abnormal methionine metabolism is involved in the pathogenesis of alcoholic liver disease was strengthened by our previous findings in a micropig model where combining dietary folate deficiency with chronic ethanol feeding produced maximal changes in these metabolites together with early onset of microscopic steatohepatitis and an eightfold increase in plasma aspartate aminotransferase. The goal of the present study was to determine potential mechanisms for abnormal levels of these methionine metabolites by analyzing the transcripts and activities of transmethylation enzymes in the livers of the same micropigs. Ethanol feeding or folate deficiency, separately or in combination, decreased transcript levels of methylenetetrahydrofolate reductase (MTHFR), methionine adenosyltransferase (MAT1A), glycine-N-methyltransferase (GNMT) and S-adenosylhomocysteine hydrolase (SAHH). Ethanol feeding alone reduced the activities of methionine synthase (MS) and MATIII and increased the activity of GNMT. Each diet, separately or in combination, decreased the activities of MTHFR and SAHH. In conclusion, the observed abnormal levels of methionine metabolites in this animal model of accelerated alcoholic liver injury can be ascribed to specific effects of ethanol with or without folate deficiency on the expressions and activities of hepatic enzymes that regulate transmethylation reactions. These novel effects on transmethylation reactions may be implicated in the pathogenesis of alcoholic liver disease.
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PMID:Hepatic transmethylation reactions in micropigs with alcoholic liver disease. 1512 59

It is a known fact that ethanol increases lipid levels in humans and experimental animals. In this study, we have investigated the effect of dendrodoine analogue (DA), DA-[4-amino-5-benzoyl-2-(4-methoxyphenylamino)-thiazole], on alcohol- and thermally oxidized sunflower oil-induced hyperlipidemia. Ethanol was given to animals at a dose of 5 ml of 20% solution and thermally oxidized sunflower oil at a level of 15% (15 g oil/100 g feed). Our results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in groups treated with alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The levels were decreased when DA was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of rats administered alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The level increased when DA was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats, whereas the activity was decreased upon DA treatment. The obtained results indicate that DA can decrease the lipid levels in alcohol- and thermally oxidized oil-treated rats.
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PMID:Role of an aminothiazole derivative on ethanol- and thermally oxidized sunflower oil-induced toxicity. 1515 74

The present work describes the protective influence of the dendrodoine analogue (DA) [4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] on thermally oxidized sunflower oil and ethanol-induced oxidative stress. Ethanol was fed to animals at a level of 20% [(7.9 g/kg body weight (bw)] and thermally oxidized sunflower oil at a level of 15% (15 mL/100 g feed). Hepatotoxicity was assessed by measuring the activity of plasma aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), which were elevated in thermally oxidized oil, and ethanol fed rats when compared with normal control rats. Tissue damage was associated with increased lipid peroxidation and disruption in the antioxidant defence mechanism in thermally oxidized oil- and ethanol-fed groups when compared with normal control group. The activity of liver marker enzymes (AST, ALP and GGT) and the level of lipid peroxidation decreased when DA was administered along with ethanol and thermally oxidized oil. The antioxidant status was near normal in DA-administered groups. Thus we propose that DA exerts antioxidant properties by modulating the activity of hepatic marker enzymes, level of lipid peroxidation and antioxidant status.
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PMID:Influence of a thiazole derivative on ethanol and thermally oxidized sunflower oil-induced oxidative stress. 1548 78

The oxidative stress induced by chronic ethanol consumption, particularly in concert with the aging process, has been implicated in changes in the structure and functions of liver cell components including membrane phospholipids. To counteract such changes, particularly those resulting from lipid peroxidation, antioxidants may be applied. Green tea contains large amounts of polyphenols, mainly catechins, which possess antioxidant properties. The aim of this study was to estimate the efficacy of green tea's influence on the physicochemical and biochemical properties of the rat liver as affected by the aging process and/or chronic ethanol intoxication. Several methods were used to evaluate this effect. Antioxidant properties were evaluated by vitamin E and antioxidant status determination. The liver trigliceride and cholesterol levels were also estimated. The extent of lipid peroxidation was determined by measuring the level of lipid peroxidation products as thiobarbituric reactive substances (TBARS). The surface charge density of the rat liver cells was measured using electrophoresis. The concentration of the marker enzymes of liver damage (alanine aminotransferase and aspartate aminotransferase) in the blood serum was also evaluated. Relative to the controls, aging was found to cause a decrease in the liver's antioxidant abilities and provoke an increase in the level of lipid peroxidation; it also increased the surface charge density of the rat liver cell membrane. Ethanol significantly aggravated these changes. This might have resulted in the liver cell membrane damage visible as a leak of alanine aminotransferase and aspartate aminotransferase into the blood. The ingestion of green tea with ethanol partially prevented these aging and/or ethanol-induced changes. Long-term drinking of green tea partially prevents the changes in the structure and function of the cell membrane caused by chronic ethanol intoxication.
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PMID:Green tea modulation of the biochemical and electric properties of rat liver cells that were affected by ethanol and aging. 1564 93

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity.
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PMID:Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity. 1610 95


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