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.