ETHANOL TREATMENT UP-REGULATES THE EXPRESSION OF MITOCHONDRIAL MANGANESE SUPEROXIDE-DISMUTASE IN RAT-LIVER

On the basis of the well-known effect of ethanol poisoning on the prooxidant/antioxidant balance of human and rodent liver we tested the response of the mitochondrial manganese-containing superoxide dismutase (MnSOD) in the liver of rats following an acute ethanol load or chronically intoxicated with an alcohol-supplemented solid diet for three weeks. In both conditions the enzyme activity and messenger RNA were monitored. In the acutely treated animals MnSOD was induced (post-)translationally already at 3 hours after ethanol injection, reached the maximum level (about 50% increment) at 9 hours and decreased thereafter. Chronic ethanol feeding caused an up-regulation of the enzyme at the mRNA level, with a good correlation between the transcript and the enzyme activity during the first two weeks of treatment. After 20 days the mRNA level dropped to normal, whereas the activity still remained high. Chronic alcohol intake also led to a significant decrease in the content of vitamin E in the liver mitochondrial and microsomal fractions, suggesting the occurence of an enhanced lipid peroxidation, consequent to the ethanol-induced oxidative stress. The response of MnSOD appears to be a protective mechanism that the genetic machinery builds up to partially overcome such a condition. (C) 1994 Academic Press, Inc.