Attenuation of serum lipid abnormalities and cardiac oxidative stress by eicosapentaenoate-lipoate (EPA-LA) derivative in experimental hypercholesterolemia

Background: Dietary cholesterol plays an important role in development of atherogenesis and cardiovascular disease. We explored the lipemic-oxidative injury in the hypercholesterolemic atherogenic animals. The effects of eicosapentaenoic acid (EPA), dl-α-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) were tested for their efficacy in controlling the atherogenic disturbances. Methods: Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Of these groups, 3 groups of rats were treated with either EPA (oral gavage, 35 mg/kg body weight/day), LA (oral gavage, 20 mg/kg body weight/day) or EPA-LA derivative (oral gavage, 50 mg/kg body weight/day) from 16th day to 30th day of the experimental period. Results: HCD induced abnormal increase in lipid peroxidation and serum cholesterol, triglyceride, LDL and VLDL, and a decreased HDL concentration. Altered activity of cardiac and serum creatine kinase, accompanied by a depressed cardiac enzymatic and nonenzymatic antioxidants defense system were observed in HCD fed rats. These changes were partially restored in the EPA and LA treated groups, however, their combined derivative EPA-LA more effectively restored the altered parameters near to that of control (P<0.05). Conclusion: Lipid abnormalities and oxidative injury were induced by a hypercholesterolemic diet. Administration of the combination treatment of EPA-LA afforded protection against the lipemic-oxidative injury.