Journal Article

N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats.

M Tariq, C Morais, S Sobki, M Al Sulaiman and A Al Khader

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 14, issue 4, pages 923-929
Published in print April 1999 | ISSN: 0931-0509
Published online April 1999 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/14.4.923
N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats.

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BACKGROUND: Cyclosporin (CsA) has played an important role in the improvement of solid-organ transplant patients and graft survival. However, nephrotoxicity due to CsA remains an important clinical challenge. The renal toxicity of CsA is attributed to reduced renal blood flow which leads to hypoxia reoxygenation injury accompanied by excessive generation of oxygen-derived free radicals (ODFR). N-acetyl-L-cysteine (NAC) is a highly potent antioxidant 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 nephrotoxicity. 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 (BUN) and serum creatinine (SCr), and kidney samples were analysed for lipid hydroperoxides, conjugated dienes and glutathione, and histopathological changes. RESULTS: Treatment of rats with CsA produced a significant increase in BUN and SCr level and histological abnormalities. CsA-induced impairment of renal toxicity was accompanied by significant increase in renal oxidative stress. NAC treatment significantly protected animals against CsA-induced structural and functional impairment of kidney. CONCLUSIONS: CsA-induced nephrotoxicity was significantly attenuated by NAC. This study clearly suggests the role of oxidative stress in the pathogenesis of CsA-induced nephrotoxicity. Concomitant use of antioxidants such as NAC to minimize CsA-induced nephrotoxicity in humans warrant further studies.

Journal Article.  0 words. 

Subjects: Nephrology

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