ABSTRACT
BACKGROUND: Cyclosporine therapy is associated with a variety of adverse effects. Recent studies have suggested increased oxidative stress as a cause of these side effects. OBJECTIVE: Since, melatonin is one of the most powerful known antioxidants, and considering that isoproterenol is one of the drugs stimulating endogenous melatonin production, we tried to determine the effect of isoproterenol on LDL susceptibility to oxidation and serum total antioxidant capacity in cyclosporine-treated rats. METHODS: 32 male Wistar rats were divided into four groups: group A were controls that received placebo; group B received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C received intravenous cyclosporine (15 mg/kg/d) alone; and group D received both drugs simultaneously at the same doses and durations-cyclosporine one week after administration of isoproterenol. Blood samples were drawn four times from rats in each group: before injections, during the treatment, end of the treatment, and one week after the last injections. RESULTS: There was a significant (p<0.05) increase in LDL susceptibility to oxidation, and a decrease in serum total antioxidant capacity (p<0.05) in group C rats. But, there were no significant changes in group B and D rats in terms of LDL susceptibility to oxidation and total antioxidant capacity. CONCLUSION: Isoproterenol may be capable of delaying adverse effects of cyclosporine by preventing the increase in LDL susceptibility to oxidation, and decrease in serum total antioxidant capacity.
ABSTRACT
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). DISCUSSION: Although cyclosporine-induced nephrotoxicity is not completely eliminated by isoproterenol, the latter showed some protective effects.
