Effect of isoproterenol on cyclosporine-induced nephrotoxicity in rat

Oxidative stress is the main mechanism resulting in cyclosporine-induced nephrotoxicity. Because of its ability to stimulate endogenous melatonin production, isoproterenol is one of the most powerful antioxidant drugs. In this study, we sought to determine the effect of isoproterenol on cyclosporine-induced nephrotoxicity in rats.

Thirty two young male Wistar rats were divided into four groups: of group A were controls that received placebo; group B, received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C, intravenous cyclosporine (15 mg/kg/d) alone; and group D, both drugs simultaneously at the same doses and durations namely cyclosporine 1 week after administration of isoproterenol. Blood samples to measure serum urea, creatinine, and melatonin levels were drawn four times for each group: before injection, at the mid period of treatment, at the end of treatment, and 1 week after the last injections.

Isoproterenol increased mean serum melatonin level in groups B and D rats (P < .05). With regard to deteriorated renal function [DRF = (urea + creatinine)/2], administration of cyclosporine with (group D) or without (group C) isoproterenol was associated with decreased renal function (P < .05), although it was more perturbed in the latter instance. Measured DRF at the middle and the end of drug administration periods of A and B (revealed significant differences compared with groups C and D; P < .05).

Although cyclosporine-induced nephrotoxicity is not completely eliminated by isoproterenol, the latter showed some protective effects.