Effect of 4-Methylpyrazole on ethanol elimination rate and hepatic redox changes in alcoholics with adequate or inadequate nutrition and in nonalcoholic controls

Abstract

Ethanol elimination rates produced by chronic alcohol consumption were higher in chronic alcoholics with adequate nutrition than in alcoholics with inadequate nutrition. 4-Methylpyrazole (4-MP, an inhibitor of alcohol dehydrogenase, ADH) at a dose of 7 mg/kg body weight inhibited ethanol elimination by 29% in nonalcoholic controls and by 35% in alcoholics with adequate nutrition, but only by 19% in alcoholics with inadequate nutrition. Galactose elimination rate (which is inhibited by NADH during ethanol oxidation) appeared to be a more sensitive indicator of hepatic redox changes than the lactate/pyruvate ratio of the peripheral venous blood. Ethanol-induced inhibition of galactose elimination was reduced in alcoholics as compared to nonalcoholic controls, and it was more reduced in alcoholics with poor nutrition than in alcoholics with adequate nutrition. Both in controls and in alcoholics, 4-MP reduced the inhibitory effect of ethanol on galactose elimination. In alcoholics with inadequate adequate nutrition, however, the further effect of 4-MP in this respect was negligible. The results indicate that the NADH reoxidation rate in chronic alcoholics is increased and support the existence, in chronic alcoholics with inadequate nutrition, of a non-ADH pathway for ethanol that does not produce reducing equivalents. In alcoholics with inadequate nutrition the proportional contribution of the ADH pathway to total ethanol elimination appears to be more decreased, resulting in reduction of the redox-mediated acute metabolic effects of alcohol.