Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiencies. Preliminary report of a new approach to pathogenesis and treatment in alcoholic liver disease.
4-Methyl pyrazole (4-MP, a specific inhibitor of alcohol dehydrogenase) reduced ethanol elimination by 30-50% and completely removed the ethanol-induced inhibition of galactose elimination in 2 control subjects. Ethanol elimination was accelerated in 2 alcoholics with adequate nutrition, but the effect of 4-MP was comparable to that in controls. In 2 other alcoholic subjects, who reported poor nutritional intake, intermediate rates of ethanol elimination were observed and 4-MP had almost no effect on ethanol or galactose elimination. These results suggest that alcohol abuse may result in an increased contribution to ethanol elimination by pathways other than that involving alcohol dehydrogenase (ADH) and that the decreased contribution from ADH, possibly potentiated by inadequate nutrition, may diminish the ethanol-induced shift in the NAD-coupled redox state. Since liver damage produced by alcohol abuse is believed to be related to changes from the normal redox state caused by ethanol, these results may explain why alcoholic liver damage is uncommon in alcoholics living on a  marginal diet. Since 4-MP effectively eliminates the ethanol-induced shift in the redox state, a therapeutic trial with 4-MP in alcoholics with a high risk for liver disease is indicated.
D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D000431:Ethanol / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009748:Nutrition Disorders / Q000209:etiology / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*
D011720:Pyrazoles; D000431:Ethanol; D005690:Galactose