Nephrology Dialysis Transplantation, Vol 14, Issue 4 923-929, Copyright © 1999 by Oxford University Press
M Tariq, C Morais, S Sobki, M Sulaiman and A Khader
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. Keywords:
cyclosporin; free radicals; glutathione; lipid peroxidation;
N-acetylcysteine; nephrotoxicity
ORIGINAL ARTICLES
N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats
Department of Nephrology and Research Centre, Armed Forces Hospital, W-912 PO Box 7897, Riyadh 11159, Saudi Arabia; Corresponding author
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