Effect of pyrazole on ethanol metabolism in ethanol-tolerant rats.
Adult male rats were pair-fed liquid diets, providing 37% of calories as ethanol or sucrose, for 1 month. Alcohol dehydrogenase (ADH) activity in the cytosol fractions of liver homogenates from the two groups did not differ with respect to total activity per 100 g body weight, Km for ethanol, or Ki for pyrazole. Other rats, fed in the same way, were fasted for 18-24 H, then given an intraperitoneal injection of pyrazole followed 1 h later by an injection of ethanol, 3g/kg. Blood alcohol curves showed an unexplained slower rise to maximum level in the chronic alcohol group. Both groups showed a period of several hours in which the blood alcohol stayed at the respective maximum concentrations, which were higher in the control group. After 7-8h the alcohol concentration began to fall in both groups, significantly more rapidly in the chronic alcohol-fed animals. A kinetic analysis shows that the results are adequately explained by the known effects of pyrazole on the ADH-mitochondrial system. The results are interpreted as evidence against the function of any microsomal ethanol oxidizing system in vivo.
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D004032:Diet; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000378:metabolism*; D005215:Fasting; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D009929:Organ Size; D010084:Oxidation-Reduction / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats
D011720:Pyrazoles; D000431:Ethanol; D000429:Alcohol Oxidoreductases