Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits

Abstract

Objectives In ex vivo and in vitro studies, it was determined that statins have antioxidative effects. The aim of the present study was to analyze the effects of hypercholesterolemic diet and atorvastatin therapy on lipid peroxidation, protein oxidation and oxidative DNA damage in rabbits. Design & Methods We determined plasma and liver tissue levels malondialdehyde (MDA) as markers of lipid peroxidation marker, plasma and liver tissue levels protein carbonyl (PCO) and total thiol (T-SH) as markers of oxidative protein damage, plasma 8-hydroxy-2-deoxyguanosine (8-OH-dG) as markers of oxidative DNA damage and erythrocyte and liver tissue levels glutathione (GSH) as markers of free radical scavengers. Twenty rabbits fed with high-cholesterol diet for 4 weeks were randomly divided into 2 groups: (1) high cholesterol diet for 4 weeks ( n = 10), and (2) the same cholesterol diet plus atorvastatin (0.3 mg/kg/day) for 4 weeks ( n = 10). A control group ( n = 5) was fed with normal diet for 8 weeks. The levels of the studied markers, except 8-OH-dG were determined by colorimetric methods. 8-OH-dG levels were measured by ELISA. Results Compared with the control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol, LDL cholesterol and oxidative stress markers, all of which were significantly reduced by atorvastatin treatment. Atorvastatin therapy has beneficial effects on decreasing protein oxidation and oxidative DNA damage related with hypercholesterolemia. Conclusion Atorvastatin reduced systemic oxidative stress in hypercholesterolemic rabbits, which might be because of its cholesterol-lowering effect and direct inhibition of protein oxidation and oxidative DNA damage in liver tissue.