Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats - Effect of vitamin E on cyclosporine nephrotoxicity

Background We report an investigation of the effects of cyclosporine (CsA) on kidney function, the glomerular synthesis of reactive oxygen species, th e peroxidation of lipids, and the levels of thromboxane B-2 (TXB2). The eff ect of the simultaneous administration of the antioxidant vitamin E (Vit E) and CsA in rats was also evaluated. Methods. Adult male Wistar rats were treated for 30 days with CsA (30 mg/kg /day), with Vit E (0.05 mg/ml), with CsA plus Vit E, or with the vehicle us ed for administration of CsA, namely 12.6% ethanol, Results. CsA induced kidney failure and increased the glomerular synthesis of superoxide anion, H2O2, malonyldialdehyde, and TXB2. Vit E minimized the adverse effects of CsA on kidney function and the glomerular synthesis of these compounds. Conclusions. Our results suggest that the acute decrease in glomerular filt ration rate induced by CsA might be mediated by the synthesis of reactive o xygen species and subsequent peroxidation of lipids, which increases the le vels of TXB2. Treatment with Vit E prevented these effects, suggesting a po ssible role for antioxidants in the prevention of CsA nephrotoxicity.