Effects of Simvastatin and Vitamin E on Diet-induced Hypercholesterolemia in Rats

Hypercholesterolemia is a dominant risk factor for the development and progression of atherosclerosis and its related cardiovascular diseases. The present study aimed to explore the effects of simvastatin combined with vitamin E on diet-induced hypercholesterolemia in rats. In the present study, hypercholesterolemia was induced by feeding rats with cholesterol-rich diet for six weeks. Rats were divided into 5 groups (n = 8): normal control, hypercholesterolemic control, simvastatin (20 mg/kg; p.o.), vitamin E (200 mg/kg; p.o.) and combination of both simvastatin and vitamin E. Drugs were given simultaneously with cholesterol-rich diet for six weeks. Diet-induced hypercholesterolemia resulted in alterations in the lipid profile markers and a state of oxidative stress coupled by compensatory increase in serum level of Nitric Oxide metabolites (NOx) and decreased aortic endothelial nitric oxide synthase (eNOS) activity parallel to increased Inducible Nitric Oxide Synthase (iNOS) activity, calcium content and aortic wall thickness. Treatment with simvastatin, vitamin E and their combination improved lipid profile and oxidative stress markers. In addition, they attenuated hypercholesterolemia-induced changes in serum NOx, aortic eNOS and iNOS activities as well as calcium content and aortic wall thickness. The results of combination therapy were better compared to simvastatin monotherapy. Pretreatment of hypercholesterolemic rats with simvastatin and vitamin E attenuated most of the changes induced in rats by cholesterol-rich die to wing to their observed anti-hyperlipidemic and antioxidant properties.