Effect of N-acetylcysteine on cisplatin induced apoptosis in rat kidney

Abstract

Purpose: Cisplatin is one of the most potent and widely used chemotherapeutic agents for the treatment of a wide variety of solid organ cancers. However, due to various side-effects such as nephrotoxicity, its therapeutic applications are limited. In the current study, it was aimed to investigate the effects of N-acetylcysteine (NAC), which is an effective antioxidant and anti-inflammatory agent, on cisplatin-induced apoptosis in rat kidneys. Materials and Methods: Twentyfour male Wistar rats were separated into 4 equal groups: Control, NAC-250, cisplatin (CP), and CP+NAC groups. Rats in the experimental groups were treated with intraperitoneally (i.p.) single-dose cisplatin (10 mg/kg) and NAC (i.p., 250 mg/kg) for 3 days. Results: At the end of the experiment, nephrotoxicity was confirmed by blood urea nitrogen and creatinine levels, and the apoptotic changes were demonstrated by TdT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3 levels in rat kidneys. The number of TUNEL-positive cells and caspase-3 levels were significantly increased by cisplatin. Treating the rats with NAC significantly decreased TUNEL-positive cells and caspase-3 levels. Conclusion: These data suggest that apoptotic cell death is involved in the pathogenesis of cisplatin-induced nephrotoxicity, and that the inhibition of apoptosis plays a central role in the beneficial effects of NAC.

Keywords

• cisplatin
• n-acetylcysteine
• apoptosis
• sisplatin
• n-asetilsistein
• apoptoz