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. 1973 Jun;134(2):507–514. doi: 10.1042/bj1340507

Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity

L Videla 1, J Bernstein 1, Y Israel 1
PMCID: PMC1177837  PMID: 16742811

Abstract

1. Administration of ethanol (14g/day per kg) for 21–26 days to rats increases the ability of the animals to metabolize ethanol, without concomitant changes in the activities of liver alcohol dehydrogenase or catalase. 2. Liver slices from rats chronically treated with ethanol showed a significant increase (40–60%) in the rate of O2 consumption over that of slices from control animals. The effect of uncoupling agents such as dinitrophenol and arsenate was completely lost after chronic treatment with ethanol. 3. Isolated mitochondria prepared from animals chronically treated with ethanol showed no changes in state 3 or state 4 respiration, ADP/O ratio, respiratory control ratio or in the dinitrophenol effect when succinate was used as substrate. With β-hydroxybutyrate as substrate a small but statistically significant decrease was found in the ADP/O ratio but not in the other parameters or in the dinitrophenol effect. Further, no changes in mitochondrial Mg2+-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg2+-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H2O2-producing system, was increased by 80–100% by chronic ethanol treatment. Oxidation of formate to CO2 in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H2O2 by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H2O2 and oxidation of ethanol by the catalase system could not account for more than 10–20% of the increased ethanol metabolism in the animals chronically treated with ethanol. 5. Results presented indicate that chronic ethanol ingestion results in a faster mitochondrial O2 consumption in situ suggesting a faster NADH reoxidation. Although only a minor change in mitochondrial coupling was observed with isolated mitochondria, the possibility of an uncoupling in the intact cell cannot be completely discarded. Regardless of the mechanism, these changes could lead to an increased metabolism of ethanol and of other endogenous substrates.

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Selected References

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