TY - JOUR
T1 - Redox state and energy metabolism during liver regeneration
T2 - Alterations produced by acute ethanol administration
AU - Gutiérrez-Salinas, José
AU - Miranda-Garduño, Luis
AU - Trejo-Izquierdo, Elizabeth
AU - Díaz-Muñoz, Mauricio
AU - Vidrio, Susana
AU - Morales-González, José A.
AU - Hernández-Muñoz, Rolando
N1 - Funding Information:
We are grateful to Dr. Mark West for his critical review of the manuscript. This work was partially supported by a grant from the Consejo Nacional de Ciencia y Tecnologı́a (CONACyT 25431-M). J.G-S is a fellow from DGAPA-UNAM, and J.A.M-G from CONACyT, México.
PY - 1999/12/1
Y1 - 1999/12/1
N2 - 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, β-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.
AB - 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, β-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.
KW - Alcohol
KW - Cell proliferation
KW - Cellular metabolism
KW - Energy charge
KW - Redox potential
UR - http://www.scopus.com/inward/record.url?scp=18144447812&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(99)00261-0
DO - 10.1016/S0006-2952(99)00261-0
M3 - Artículo
SN - 0006-2952
VL - 58
SP - 1831
EP - 1839
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -