title: Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil.
abstract: Increased hepatic oxidative stress with ethanol administration is hypothesized to be caused either by enhanced pro-oxidant production or decreased levels of antioxidants or both. We used the intragastric feeding rat model to assess the relationship between hepatic antioxidant enzymes and pathological liver injury in animals fed different dietary fats. 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 group: liver pathology, lipid peroxidation, manganese superoxide dismutase (MnSOD) levels, copper-zinc SOD (CuZnSOD) levels, glutathione peroxidase (GPX) levels, and catalase (CAT) levels. All enzymes were evaluated using activity assays and immunoblots. Rats fed FE showed the most severe pathology (fatty liver, necrosis, and inflammation), those fed CE showed moderate changes, those fed PE showed fatty liver only, and those fed MCTE were normal. Parameters indicative of lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances) were also greater in rat livers from animals fed the diets high in polyunsaturated fatty acids (CE and FE). CuZnSOD, GPX, and CAT activities showed an inverse correlation (r=-.92, P < .01) with severity of pathological injury, with the lowest levels for both enzymes found in FE-fed rats. Decreased enzyme activity in CE- and FE-fed rats was accompanied by similar decreases in immunoreactive protein. Ethanol administration did not cause significant decreases in enzyme activity in groups that showed no necroinflammatory changes (MCTE and PE). MnSOD activity showed no significant change in any ethanol-fed group. Our results show that decreases in CuZnSOD, GPX, and CAT occur in rats showing pathological liver injury and also having the highest levels of lipid peroxidation. These results suggest that feeding dietary substrates that enhance 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 polyunsaturated fatty acids and ethanol could possibly increase the susceptibility to oxidative damage and further contribute to ethanol-induced liver injury.
authors.affiliation: Department of Pharmacology, Pennsylvania State University, Hershey, USA.
authors.forename: R
authors.initials: R
authors.lastname: Polavarapu
authors.forename: D R
authors.initials: DR
authors.lastname: Spitz
authors.forename: J E
authors.initials: JE
authors.lastname: Sim
authors.forename: M H
authors.initials: MH
authors.lastname: Follansbee
authors.forename: L W
authors.initials: LW
authors.lastname: Oberley
authors.forename: A
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: A A
authors.initials: AA
authors.lastname: Nanji
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003314:Corn Oil; D004041:Dietary Fats / Q000378:metabolism*; D005395:Fish Oils; D005979:Glutathione Peroxidase / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; D005395:Fish Oils; D008054:Lipid Peroxides; D003314:Corn Oil; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase