Protective effect of lipoic acid on oxidative and peroxidative damage in cyclosporine A-induced renal toxicity

Abstract

Free radical generation, including reactive nitrogen and reactive oxygen species, is known to participate in cell physiology in both a positive and negative manner. Moreover, alterations in their concentrations are implicated in a number of renal diseases. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation, is capable of causing lipid peroxidation and protein oxidation in cyclosporine A (CsA) induced cellular damage. The present study was conducted to investigate the possible protective role of Lipoic acid (LA) in nitric oxide mediated cellular abnormalities induced by CsA in rat kidney. Adult male albino rats of Wistar strain were given CsA at a dose of 25 mg/kg body weight, orally for 21 days. An extensive elevation in the activities of xanthine oxidase was noted in the renal tissue of the CsA administered rats. These changes were associated with significant increase in the levels of plasma lipid peroxidation with high protein carbonyl contents and 3-nitrotyrosine formation coupled with diminished protein thiols. In addition, plasma nitrite/nitrate (NO(x)), RT-PCR for inducible NOS (iNOS) mRNA, and immunohistochemically demonstrable iNOS protein were evaluated to assess peroxidative damage. Concomitant treatment with LA (20 mg/kg body weight, orally for 21 days showed that the oxidative stress alteration were significantly decreased in CsA treated renal tissue. While the expression of iNOS and the amounts of NO(x) were decreased simultaneously. These results indicate that the antioxidant LA might have a protective effect against CsA-induced peroxidative changes and cellular damage of the renal tissue of the rat.