Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inability of the 'ethanol/high vitamin A Lieber-DeCarli diet' to induce liver fibrosis in two different rat strains was further evaluated by determining changes in parameters of liver cell damage and of retinoid and lipid metabolism. In the ethanol/vitamin A-treated group, slight but constant hepatic cell damage, as indicated by elevated alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities in blood, was already observed at 6 months and maintained until the time of death at 16 months. Serum gamma-glutamyl transaminase activities were not raised. Moderate parenchymal liver cell damage was not accompanied by fibrosis. Hypertriglyceridemia or hypercholesterolemia were observed at 6-16 months of chronic alcohol administration. This response was strain dependent. In ethanol-treated rats of both strains, total liver retinoids and serum retinol concentrations were not altered. Therefore, the hypothesis that interaction between alcohol and retinoids is a major factor in the pathogenesis of alcoholic liver disease, needs to be reconsidered.
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PMID:Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 2. Biochemical observations. 174 28

Experiments were conducted on 128 male rats kept on a retinol-deprived diet during 12-14 weeks, that resulted in vitamin A deficiency. The content of phospholipids, total lipids, proteins and the activity of esterase, glutamate dehydrogenase, catalase, glutathione-S-transferase, aldehyde dehydrogenase and aldehyde oxidase were assayed in the bronchoalveolar lavage fluid, in homogenates and microsomes of the lungs. The content of phospholipids in the bronchoalveolar lavage fluid was reduced up to 63.9%, as compared to that in the control rats, while the protein content was unchanged. The levels of phospholipids, total lipids and protein rose in the homogenates and microsomes of the lungs. Esterase activity decreased up to 38.6% of the control level, catalase--up to 73.2%, glutamate dehydrogenase--up to 79%. There was a tendency to decrease in glutathione-S-transferase activity, while aldehyde dehydrogenase and aldehyde oxidase activities remained unchanged. It is suggested that the disorders in the enzymatic activity and lipid content in the surfactant can be responsible for the changes in the xenobiotic biotransformation and for the rise in xenobiotic toxicity.
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PMID:[Effect of vitamin A deficiency on surfactants and enzymes of xenobiotic metabolism in the rat lung]. 367 17

To study the possible hepatotoxicity of vitamin A supplementation and its potentiation by ethanol, rats were fed diets with either normal or fivefold increased vitamin A content, both with or without ethanol. Ethanol with a normal vitamin A diet produced the expected proliferation of the smooth endoplasmic reticulum and moderate mitochondrial lesions. Vitamin A supplementation by itself produced endoplasmic reticulum proliferation, slight enlargement of mitochondria, and moderate decrease in cytochrome oxidase activity and cytochrome aa3 content. The combination of high vitamin A and ethanol resulted in much more striking lesions, with giant mitochondria containing paracrystalline inclusions and depression of oxygen consumption in state-3 respiration with five different substrates, including palmitate and palmitoyl coA. The depression of fatty acid oxidation may have contributed to the lipid accumulation. The blood levels of vitamin A were unaffected whereas liver levels of vitamin A were increased by vitamin A supplementation and decreased by ethanol. As a net result the liver vitamin A content of the high-A-ethanol groups was not greater than that of the normal-A-control group, suggesting that a metabolite of vitamin A rather than vitamin A itself may have been responsible for the potentiation of vitamin A toxicity by ethanol. Mitochondrial toxicity reflected itself also in decreased content of various cytochromes and reduced activity of enzymes, including glutamate dehydrogenase. The activity of the latter was increased in the serum. Implications of these findings for the routine treatment of alcoholics with vitamin A and the monitoring for possible signs of toxicity are discussed.
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PMID:Hepatotoxicity of vitamin A and ethanol in the rat. 627 29

Rats were fed up to 9 months diets supplemented with vitamin A in an amount that, by itself, had no apparent adverse effect on the liver. When associated with chronic ethanol administration, vitamin A supplementation strikingly exacerbated ethanol-induced abnormalities: fat accumulation was increased and numerous giant mitochondria were observed. Furthermore, lesions appeared which ethanol alone does not produce in rats, namely necrosis, inflammation, and fibrosis. Vitamin A supplementation increased the number of fat storing cells (lipocytes) which positively correlated with vitamin A accumulation in the liver. However, when vitamin A supplementation was combined with ethanol administration, vitamin A levels in the liver and the number of fat storing cells decreased and numerous myofibroblasts appeared in association with abundant collagen fibers. There was also hepatic inflammation and necrosis, accompanied by a rise in serum glutamate dehydrogenase, SGOT, and SGPT and a decrease in retinol binding protein and vitamin A. We conclude that amounts of vitamin A, which by themselves appear harmless, may produce severe liver lesions when associated with chronic ethanol consumption.
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PMID:Hepatic fibrosis after long-term administration of ethanol and moderate vitamin A supplementation in the rat. 668 8