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 administration in drinking water as a model of moderate alcohol intoxication. Our results show a slight decrease in liver cytochrome aa3 content, the mitochondrial alteration which is most consistently observed during chronic ethanol feeding. In liver and heart mitochondria, ethanol consumption led to an increase in state 3 respiration with NAD(+)-linked substrates, whereas no changes were apparent in respiration rates with succinate as substrate. However a decrease was found in state 3 respiration with succinate in brain mitochondria isolated from ethanol-fed rats. Submitochondrial particles (SMP) were used to study the superoxide radical (O2-.) production at the level of antimycin-inhibited regions of the respiratory chain. It appears that there is no clear correlation between ethanol effects on respiration and O2-. production. Whereas O2-. generation remained unchanged in heart mitochondria, an elevation of O2-. generation was observed in brain mitochondria, and in contrast, the rate of O2-. production was decreased in liver mitochondria of the ethanol-group in comparison to the control-group. Our findings support a tissue specificity for the toxic effects of ethanol towards the mitochondria and indicate that mitochondrial free radical mechanisms are involved in ethanol-induced toxicity in the brain.
Ribiere
C
C
Department of Biomedical Research on Alcoholism, Faculté de Médecine, Paris, France.
Hininger
I
I
Saffar-Boccara
C
C
Sabourault
D
D
Nordmann
R
R
D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D000431:Ethanol