CYCLOSPORINE-A NEPHROTOXICITY - ROLE OF THROMBOXANE AND REACTIVE OXYGEN SPECIES

The main adverse effect of cyclosporine A (CyA) is nephrotoxicity. CyA increases urinary concentrations of thromboxane A(2) (TXA(2)), a pote nt vasoconstrictor that can be involved in kidney failure induced by C yA. Furthermore, it has been postulated that a relationship exists bet ween oxygen free radicals and the synthesis of arachidonate metabolite s in experimental models of CyA nephrotoxicity. We studied the effect of vitamin E (VitE), an oxygen free radical scavenger, on renal functi on, on glomerular synthesis of thromboxane B-2 (TXB2), and on free rad icals in rats treated with CyA. Four groups of male Wistar rats were s tudied: (1) a control group; (2) a group given VitE at 0.05 mg/dl in d rinking water for 25 days; (3) a group given CyA at 50 mg/kg body weig ht/day orally for 10 days; and (3) a group given Vit E + CyA, in which rats were provided with drinking water containing VitE for 15 days an d afterwards were treated with VitE and CyA for 10 days. Renal functio n parameters and glomerular synthesis of TXB2, superoxide anion (O-2 . (-)), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were evaluat ed. CyA decreased body weight, caused deterioration of kidney function and increased glomerular synthesis of TXB2, O-2 .(-), MDA, and H2O2. Pretreatment with VitE prevented the effects of CyA on kidney function and decreased glomerular synthesis of these mediators. In conclusion, CyA induced glomerular synthesis of reactive oxygen species (ROS) and TxB(2). Pretreatment with VitE inhibited acute renal failure induced by CyA, probably by scavenging free radicals and by inhibiting the syn thesis of TXB2.