Hepatic mitochondrial oxidative metabolism and lipid peroxidation in iron-loaded rats fed ethanol.
The aims of this study were to determine whether chronic ethanol consumption potentiates mitochondrial lipid peroxidation or impairment of mitochondrial oxidative metabolism in rats with chronic iron overload. Experimental iron overload was induced by feeding rats a chow diet supplemented with 2.5% carbonyl iron. After 8 to 12 weeks, half of the iron-loaded and control animals were changed to a liquid diet containing ethanol for 4 to 5 weeks. The remaining animals were fed an isocaloric amount of diet containing dextrin-maltose instead of ethanol for 4 to 5 weeks. Iron-supplemented animals had a 20-fold increase in hepatic iron concentration as compared with controls. Iron and ethanol independently increased plasma alanine aminotransferase (ALT) levels (p < 0.05) while the combination resulted in an additive increase in ALT levels (p < 0.01). Although iron overload increased the levels of mitochondrial conjugated dienes and significantly reduced the mitochondrial respiratory control ratio, ethanol administration did not affect these parameters in animals with or without iron overload. Livers from iron-loaded rats that received ethanol showed mild to moderate steatosis with 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 iron-loaded rats, as evidenced by an increase in plasma ALT level. However, there were no additive or synergistic effects of iron and ethanol on either mitochondrial lipid peroxidation or mitochondrial oxidative metabolism.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D000431:Ethanol / Q000494:pharmacology*; D007501:Iron / Q000032:analysis / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D007501:Iron; D000410:Alanine Transaminase