N-acetylcysteine attenuates cyclosporine-induced nephrotoxicity in male albino rats

ABSTRACT

Cyclosporine A [Cs A] is used for the treatment of autoimmune and inflammatory disorders. However, Cs A-induced nephrotoxicity remains an important clinical problem, and oxidative stress has been implicated as a possible responsible mechanism. We assessed the protective ability of N-acetylcysteine [NAC], an antioxidant, against Cs A-induced nephrotoxicity. Thirty adult male albino rats were used to study the effect of cyclosporine [Cs A] and the action of N-acetylcysteine [NAC] on certain renal parameters; Blood Urea Nitrogen [BUN] and creatinine. Malondialdehyde [MDA] and catalase [CAT] levels were used as biomarker for testing the antioxidant potential of the drug. Endothelin-l[ET-l] levels were estimated in plasma. Animals were randomly assigned into three groups. Group I rats as control, group 2 were treated with Cs A and group 3 with Cs A plus NAC. Cs A administration for 21 days produced elevated levels of MDA and decreased in antioxidant enzyme CAT and deteriorated the renal function as assessed by increased serum Blood Urea Nitrogen [BUN] and creatinine. Plasma ET-l was also elevated as compared to control groups. Oral administration of NAC [140 mg/kg/day] significantly attenuated renal dysfunction, reduced elevated levels of MDA, increased the level of CAT and decreased level of ET- 1. These results indicate that NAC produces a protective mechanism against Cs A-induced nephrotoxicity in rats and suggest a role of Cs A for oxidative stress and the nephroprotective role of NAC against Cs A-induced nephrotoxicity in rats