N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats

Tariq, M, Morais, C, Sobki, S, Al Sulaiman, M and Al Khader, A (1999) N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrology Dialysis Transplantation, 14 4: 923-929. doi:10.1093/ndt/14.4.923


Author Tariq, M
Morais, C
Sobki, S
Al Sulaiman, M
Al Khader, A
Title N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats
Journal name Nephrology Dialysis Transplantation   Check publisher's open access policy
ISSN 0931-0509
1460-2385
Publication date 1999-04
Sub-type Article (original research)
DOI 10.1093/ndt/14.4.923
Volume 14
Issue 4
Start page 923
End page 929
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
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.
Keyword Cyclosporin
Free radicals
Glutathione
Lipid peroxidation
N-acetylcysteine
Nephrotoxicity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Mon, 20 Dec 2010, 13:59:13 EST