Redox state and energy metabolism during liver regeneration - Alterations produced by acute ethanol administration

Ethanol metabolism can induce modifications in liver metabolic pathways tha t are tightly regulated through the availability of cellular energy and thr ough the redox state. Since partial hepatectomy (PH)-induced liver prolifer ation requires an oversupply of energy for enhanced syntheses of DNA and pr oteins, the present study was aimed at evaluating the effect of acute ethan ol administration on the PH-induced changes in cellular redox and energy po tentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of la ctate, pyruvate, P-hydroxybutyrate, acetoacetate, and adenine nucleotides l ed us to estimate the cytosolic and mitochondrial redox potentials and ener gy parameters. Specific activities in the liver of alcohol metabolizing enz ymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the firs t 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotox in readily blocked the PH induced changes in the cellular redox state. In a ddition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment p revented the PH-induced diminution of ADH activity. In summary, our data su ggest that ethanol could minimize the PH-promoted metabolic adjustments med iated by redox reactions, probably leading to an ineffective preparatory ev ent that culminates in compensatory liver growth after PH in the rat. BIOCH EM PHARMACOL 58;11:1831-1839, 1999. (C) 1999 Elsevier Science Inc.