INCREASED LIPID-PEROXIDATION AND IMPAIRED ANTIOXIDANT ENZYME FUNCTIONIS ASSOCIATED WITH PATHOLOGICAL LIVER-INJURY IN EXPERIMENTAL ALCOHOLIC LIVER-DISEASE IN RATS FED DIETS HIGH IN CORN-OIL AND FISH-OIL

Increased hepatic oxidative stress with ethanol administration is hypo thesized to be caused either by enhanced pro-oxidant production or dec reased levels of antioxidants or both. We used the intragastric feedin g rat model to assess the relationship between hepatic antioxidant enz ymes and pathological liver injury in animals fed different dietary fa ts. Male Wistar rats (5 per group) were fed ethanol with either medium -chain triglycerides (MCTE), palm oil (PE), corn oil(CE), or fish oil (FE), Control animals were fed isocaloric amounts of dextrose instead of ethanol with the same diets. The following were evaluated in each g roup: liver pathology, lipid peroxidation, manganese superoxide dismut ase (MnSOD) levels, copper-zinc SOD (CuZnSOD) levels, glutathione pero xidase (GPX) levels, and catalase (CAT) levels. All enzymes were evalu ated using activity assays and immunoblots, Rats fed FE showed the mos t severe pathology (fatty liver, necrosis, and inflammation), those fe d CE showed moderate changes, those fed PE showed fatty liver only, an d those fed MCTE were normal. Parameters indicative of lipid peroxidat ion (conjugated dienes and thiobarbituric acid-reactive substances) we re also greater in rat livers from animals fed the diets high in polyu nsaturated fatty acids (CE and FE). CuZnSOD, GPX, and CAT activities s howed an inverse correlation (r = -.92, P < .01) with severity of path ological injury, with the lowest levels for both enzymes found in FE-f ed rats. Decreased enzyme activity in CE-and FE-fed rats was accompani ed by similar decreases in immunoreactive protein. Ethanol administrat ion did not cause significant decreases in enzyme activity in groups t hat showed no necroinflammatory changes (MCTE and PE), MnSOD activity showed no significant change in any ethanol-fed group. Our results sho w that decreases in CuZnSOD, GPX, and CAT occur in rats showing pathol ogical liver injury and also having the highest levels of lipid peroxi dation, These results suggest that feeding dietary substrates that enh ance lipid peroxidation can exacerbate both ethanol-induced oxidative damage as well as necroinflammatory changes. The decrease in activity of antioxidant enzymes observed in animals fed diets high in polyunsat urated fatty acids and ethanol could possibly increase the susceptibil ity to oxidative damage and further contribute to ethanol-induced live r injury.