Protective role of eicosapentaenoate-lipoate (EPA-LA) derivative in combating oxidative hepatocellular injury in hypercholesterolemic atherogenesis.

The aim of the present study is to evaluate the effect of eicosapentaenoic acid (EPA), dl-alpha-lipoic acid (LA) and eicosapentaenoate-lipoate (EPA-LA) derivative on the atherogenic disturbances in hypercholesterolemic atherogenic animals. Eight groups of male Wistar rats were employed in this study, wherein four groups were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days, among which, three groups of rats were also treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) commencing from 16th day of the experimental period. The remaining four groups served as control and EPA, LA and EPA-LA derivative treated drug controls. Abnormal increases in the levels of malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxyguanosine, as well as depressed antioxidants status, were observed in hepatic tissue of HCD fed rats. HCD induced abnormal elevation in the activities of hepatic lactate dehydrogenase, aminotransferases and alkaline phosphatase (ALP) and was accompanied by increased hepatic cholesterol level and altered fatty changes in the histology of liver. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats. The results of this study present oxidative injury induced by hypercholesterolemic diet and administration of the combination treatment of EPA-LA afforded sound protection against lipemic-oxidative injury.