VITAMIN-E TREATMENT ABOLISHES CYCLOSPORIN E-A NEPHROTOXICITY

Reactive oxygen species have been implicated in cyclosporine A (CyA) n ephrotoxicity directly or through the activation of the lipid peroxida tion process. We have previously demonstrated that CyA increases glome rular synthesis and urinary excretion of tromboxoxane B-2 (TXB2) in ra ts. Our aim was to analyze the effects of VitE (alpha-tocoferol) on ki dney function, lipid peroxidation and glomerular synthesis of hydrogen peroxide (HPO) in isolated rat kidney glomeruli of rats treated with CyA. Male Wistar rats weighting 250-275 g were treated with oral CyA ( 30 mg/kg/day) for 30 days. In another group, rats drank water suppleme nted with VitE (0.05 mg/dl) and were treated with CyA (30 mg/kg/day). Results were compared with a control group and a group treated only wi th VitE. We determined malonyldialdehyde (MDA) in serum. Furthermore, in isolated glomeruli we analized MDA, HPO (by the peroxidase red pehn ol method) and TXB2 (by radioimmunoassay). CyA induced kidney failure and increased serum MDA. CyA also increased glomerular synthesis of th ese mediators. We concluded that CyA caused deterioration in kidney fu nction and increased glomerular synthesis of reactive oxigen species, lipid peroxidation and TXB VitE inhibited these effects suggesting a r ole of tree radicals, probably through the induction of lipid peroxida tion and subsequent synthesis of TXB2 in CyA nephrotoxocity.