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.