Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Different types of dietary fat were administered [saturated fat (SE), corn oil (CE) and fish oil (FE)] with ethanol to induce varying severities of liver injury. Ethanol-fed rats were pair-fed with dextrose-fed controls that received isocaloric amounts of dextrose. All animals were killed at 1 month and the following studies were carried out: evaluation of severity of pathologic liver injury, mRNA quantitation for catalase, glutathione peroxidase (GPx), and manganese superoxide dismutase (MnSOD), microsomal conjugated dienes, and hydrogen peroxide. SE animals had no liver injury, FE animals had severe liver injury, and CE animals had moderate liver injury. Ethanol induced GPx mRNA in all dietary groups, with the highest levels seen in the FE group. The pattern of catalase mRNA induction was similar to that of GPx mRNA. In contrast, MnSOD mRNA was decreased compared to controls in animals that developed pathologic liver injury, i.e., CE and FE groups. A positive correlation was seen between conjugated diene levels and GPx mRNA (r = 0.88, P < 0.01) and catalase mRNA. The similar slopes for the relationship between conjugated dienes and catalase in the fish oil and non-fish oil groups indicate that the same degree of lipid peroxidation increases catalase mRNA to a greater degree in fish oil-fed rats. A positive correlation was also seen between catalase mRNA and H₂O₂ (r = 0.95, P < 0.001). We propose that the increase in catalase and GPx mRNA levels is probably in response to enhanced lipid peroxidation; the decrease in MnSOD mRNA may predispose the cells to liver injury.