RESUMO
Cydosporin A [CyA] is the immunosuppressant most frequently used in transplant surgery and in the management of autoimmune diseases. CyA-induced oxidative stress together with dyslipidemia have been implicated in the pathogenesis of vascular dysfunction associating CyA therapy. The present study investigated the possible protective effect of simvastatin, a lipid-lowering drug with potent antioxidant properties, against CyA-induced endothelial damage in male rats. Eighteen male Wistar rats were used. They were divided into 3 groups: control, CyA and CyA + simvastatin. In the control group, rats were administered the vehicle, olive oil; in the CyA group, rats were administered CyA [20 mg/kg/day, s.c. for 14 days] and in the CyA+simvastatin group, rats were co-administered simvastatin [2.5 mg/kg/day, s.c. for 14 days] and CyA. Administration of CyA [20 mg/kg/day, s.c. for 14 days] in male rats resulted in a significant increase in the lipid peroxidation product, malondialdehyde [MDA], and a significant decrease in superoxide dismutase [SOD] activity in plasma. CyA treatment was also associated with a significant increase in plasma nitrite level as well as an elevation in plasma cholesterol, triglycerides [TGs], low density lipoproteins [LDL] and a reduction in high density lipoproteins [HDL] levels. CyA-induced vascular dysfunction was further confirmed by the attenuation of endothelium-dependent relaxations produced by carbachol in rat isolated aortic rings. Co-administration of simvastatin [2.5 mg/kg/day, s.c. for 14 days] with CyA significantly reversed the deleterious biochemical and functional vascular effects that accompanied CyA treatment. The present study provides good evidence that both oxidative stress and dyslipidemia underlie the CyA-induced vascular damage, an effect that could be reversed by simvastatin co-administration