Effect of propranolol on ethanol metabolism-evidence for the role of mitochondrial NADH oxidation.

Ethanol metabolism in the rat as measured in vivo by ¹⁴CO₂ production or in vitro by the removal of ethanol by liver slices was inhibited approximately 30 per cent by propranolol. There was no inhibitory effect of propranolol on rat liver alcohol dehydrogenase, catalase. NADPH-dependent microsomal ethanol oxidation or formate oxidation to ¹⁴CO₂. Propranolol inhibited fatty acid oxidation to ¹⁴CO₂in vivo as well as by liver slices and isolated hepatic mitochondria. NADH oxidation by hepatic mitochondria was also reduced by propranolol. 2,4-Dinitrophenol treatment or chronic ethanol feeding of rats stimulated alcohol metabolism as well as hepatic mitochondrial NADH oxidation. These increases were abolished by propranolol. The effect of propranolol in blocking the increase in ethanol oxidation after chronic alcohol feeding appears to be related to its action on the mitochondrial re-oxidation of NADH to NAD. Propranolol inhibits mitochondrial NADH oxidation, while 2,4-dinitrophenol or chronic ethanol feeding stimulates this process. The present studies support the concept that the rate of hepatic ethanol metabolism is limited, at least in part, by the mitochondrial oxidation of NADH.