Metabolic Interaction of Ethanol and Alprenolol in Isolated Liver Cells

Abstract

Abstract: Metabolism of ethanol and alprenolol was studied in isolated rat liver cells. At low ethanol concentrations, where the rate of ethanol metabolism seemed to be limited by the rate of re‐oxidation of NADH, ethanol metabolism was markedly stimulated by the addition of alprenolol, propranolol or hexobarbital. At higher concentrations of ethanol no stimulation by added alprenolol was observed. Alprenolol‐stimulated ethanol metabolism was more sensitive to low concentrations of the ADH inhibitor 4‐CH3‐pyrazole, than unstimulated ethanol metabolism. Alprenolol metabolism in isolated liver microsomes and isolated liver cells was inhibited by addition of ethanol; however, at very low ethanol concentrations a slight stimulation of alprenolol metabolism was observed in isolated liver cells. The increased lactate/pyruvate ratio caused by ethanol metabolism in isolated liver cells was decreased by the addition of alprenolol. The present findings indicate that during simultaneous metabolism of ethanol and alprenolol, at low concentrations of ethanol, electrons can be diverted from the greatly reduced NADH/NAD+ couple by the microsomal monooxygenase reaction.