MITOCHONDRIAL RESPIRATORY ACTIVITY AND SUPEROXIDE RADICAL GENERATION IN THE LIVER, BRAIN AND HEART AFTER CHRONIC ETHANOL INTAKE

Functional characteristics of mitochondria isolated from liver, brain and heart were studied in ethanol-fed rats using ethanol administratio n in drinking water as a model of moderate alcohol intoxication. Our r esults show a slight decrease in liver cytochrome aa(3) content, the m itochondrial alteration which is most consistently observed during chr onic ethanol feeding. In liver and heart mitochondria, ethanol consump tion led to an increase in state 3 respiration with NAD(+)-linked subs trates, whereas no changes were apparent in respiration rates with suc cinate as substrate. However a decrease was found in state 3 respirati on with succinate in brain mitochondria isolated from ethanol-fed rats . Submitochondrial particles (SMP) were used to study the superoxide r adical (O-2 radical anion) production at the lever of antimycin-inhibi ted regions of the respiratory chain. It appears that there is no clea r correlation between ethanol effects on respiration and O-2 radical a nion production. Whereas O-2 radical anion generation remained unchang ed in heart mitochondria, an elevation of O-2 radical anion generation was observed in brain mitochondria, and in contrast, the rate of O-2 radical anion production was decreased in liver mitochondria of the et hanol-group in comparison to the control-group. Our findings support a tissue specificity for the toxic effects of ethanol towards the mitoc hondria and indicate that mitochondrial free radical mechanisms are in volved in ethanol-induced toxicity in the brain.