HEPATIC MITOCHONDRIAL OXIDATIVE-METABOLISM AND LIPID-PEROXIDATION IN IRON-LOADED RATS FED ETHANOL

The aims of this study were to determine whether chronic ethanol consu mption potentiates mitochondrial lipid peroxidation or impairment of m itochondrial oxidative metabolism in rats with chronic iron overload. Experimental iron overload was induced by feeding rats a chow diet sup plemented with 2.5% carbonyl iron, After 8 to 12 weeks, half of the ir on-loaded and control animals were changed to a liquid diet containing ethanol for 4 to 5 weeks. The remaining animals were fed an isocalori c amount of diet containing dextrin-maltose instead of ethanol for 4 t o 5 weeks, Iron-supplemented animals had a 20-fold increase in hepatic iron concentration as compared with controls, Iron and ethanol indepe ndently increased plasma alanine aminotransferase (ALT) levels (p < 0. 05) while the combination resulted in an additive increase in ALT leve ls (p < 0.01). Although iron overload increased the levels of mitochon drial conjugated dienes and significantly reduced the mitochondrial re spiratory control ratio, ethanol administration did not affect these p arameters in animals with or without iron overload. Livers from iron-l oaded rats that received ethanol showed mild to moderate steatosis wit h scattered necroinflammatory foci, There was no significant increase in necroinflammatory foci in the livers of the iron plus ethanol group as compared with the iron group. In conclusion, we have demonstrated an additive increase in hepatocellular injury when ethanol is fed to i ron-loaded rats, as evidenced by an increase in plasma ALT level, Howe ver, there were no additive or synergistic effects of iron and ethanol on either mitochondrial lipid peroxidation or mitochondrial oxidative metabolism.