The Role of Mitochondrial NADH Reoxidation in the Hepatic Metabolism of Ethanol: Studies with Perfused Livers from Ethanol and CCl4-Treated Rats

Abstract

The effect of ethanol and CCl4 treatments on alcohol dehydrogenase (ADH) dependent metabolism of ethanol was assessed employing a non-recirculating hemoglobin-free liver perfusion system. The administration of one large dose of ethanol (5 g/kg) nearly doubled hepatic O2 and ethanol uptakes within 2.5 hrs. This Swift Increase in Alcohol metabolism (SIAM) may be explained as follows: Ethanol produces a stress reaction which leads to a increase in circulating catecholamine. This in turn activates glycogenolysis leading to decreased ATP synthesis by glycolysis. Ultimately ADP not phosphorylated via the anaerobic pathway activates O2 uptake. This sequence of events then stimulates ethanol metabolism by providing more NAD+ for the ADH reaction. In another experimental series, acute and chronic CCl4 treatments decreased hepatic ethanol uptake as well as O2 consumption approximately 50 % and 70 %, respectively. CCl4 treatment did not significantly alter hepatic ADH activity but changed mitochondrial NADH oxidation in both groups significantly. The present results clearly indicate that the mitochondrial NADH reoxidation system plays a major role determining rates of hepatic metabolism of ethanol.