N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats

Background. Cyclosporin(CsA) has played an important role in the improvemen t of solid-organ transplant patients and graft survival. However, nephrotox icity due to CsA remains an important clinical challenge. The renal toxicit y of CsA is attributed to reduced renal blood flow which leads to hypoxia-r eoxygenation injury accompanied by excessive generation of oxygen-derived f ree radicals (ODFR). N-acetyl-L-cysteine (NAC) is a highly potent antioxida nt that has been shown to reduce ODFR injury. In this study an attempt was made to assess the effect of NAC on CsA-induced lipid peroxidation and neph rotoxicity. Methods. Adult Sprague-Dawley rats were treated orally with CsA (25 and 50 mg/kg) alone and in combination with different doses of NAC (10, 20 and 40 mg/kg) for a period of 3 weeks. Twenty-four hours after the last treatment, animals were sacrificed and blood was analysed for blood urea nitrogen (BU N) and serum creatinine (SCr), and kidney samples were analysed for lipid h ydroperoxides, conjugated dienes and glutathione, and histopathological cha nges. Results. Treatment of rats with CsA produced a significant increase in BUN and SCr level and histological abnormalities. CsA-induced impairment of ren al toxicity was accompanied by significant increase in renal oxidative stre ss. NAC treatment significantly protected animals against CsA-induced struc tural and functional impairment of kidney. Conclusions. CsA-induced nephrotoxicity was significantly attenuated by NAG . This study clearly suggests the role of oxidative stress in the pathogene sis of CsA-induced nephrotoxicity. Concomitant use of antioxidants such as NAC to minimize CsA-induced nephrotoxicity in humans warrant further studie s.