Redox state and energy metabolism during liver regeneration: alterations produced by acute ethanol administration.
Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes 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 first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.
Gutiérrez-Salinas
J
J
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México D.F.
Miranda-Garduño
L
L
Trejo-Izquierdo
E
E
Díaz-Muñoz
M
M
Vidrio
S
S
Morales-González
J A
JA
Hernández-Muñoz
R
R
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol