Effects of chronic ethanol treatment and thyroxine administration on ethanol metabolism and liver oxidative capacity.
Chronic administration of ethanol to rats leads to an increase in the rate of ethanol metabolism in vivo and in vitro. In vitro studies in liver slices showed that ouabain, an inhibitor of the Na++K+-activated adenosine triphosphatase, can completely block the extra ethanol metabolism in the livers of the treated animals only in the presence of ouabain. Administration of thyroxine led to an increase in the rate of ethanol metabolism when measured both in vitro and in vivo. This effect was biphasic; an activation occurred only with low doses of thyroxine but disappeared after administration of larger doses. Alcohol dehydrogenase activity in the liver of the animals treated with large doses of thyroxine was found to be significantly reduced. With the doses used (50-1000 mug/kg), thyroxine also increased the rate of oxygen consumption as measured in liver slices. However, a biphasic effect did not occur; a near maximum activation on the rate of oxygen consumption occurred with low doses of thyroxine (100 mug/kg). Oxygen consumption was also found to be increased in the liver of animals chronically treated with ethanol. A maximal effect was produced after 18 to 21 days of treatment. For both ethanol and thyroxine-treated animals, an increased rate of oxygen consumption occurred with a concomitant loss of dinitrophenol effect. Mitochondrial alpha-glycerophosphate oxidase was found to be increased in the liver of animals treated with ethanol or with thyroxine. In these two groups, this enzymatic activity appeared to be less affected by the treatment than the dinitrophenol-activated respiration.
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013974:Thyroxine / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D004140:Dinitrophenols; D000431:Ethanol; D010042:Ouabain; D000429:Alcohol Oxidoreductases; D005993:Glycerolphosphate Dehydrogenase; D013974:Thyroxine