Possible protective activity of n‑acetyl cysteine against cisplatin‑induced hepatotoxicity in rats

Abstract

CP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic efects. The present study aimed to reveal the efects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological fndings. Twenty-eight wistar rats were randomly divided into four groups of seven animals. A dose of saline was administered (i.p.) to the control group for 5 days. One dose of NAC (200 mg/kg) was administered to the NAC group for 5 days (i.p.). To the NAC + CP group, a dose of CP (7.5 mg/kg) was administered on days 2 and 5 of the experiment, a dose of NAC (200 mg/ kg) (i.p.) was administered for 5 day of the experiment. CP (7.5 mg/kg) was administered to the CP group on days 2 and 5 of the experiment. At the end of the experiment, the biochemical, histological, and mRNA expression analyses of the liver tissues isolated from all the rats were performed. A statistically signifcant decrease was observed in the AST and ALT enzyme activities in Group NAC + CP compared to Control and CP groups. In addition, it was determined that the NAC administration reduced CPinduced infammation by increasing the level of NF-κB and decreased CP-caused oxidative stress by decreasing the GPx level. Moreover, the histopathological analyses showed that NAC improved liver morphology. It was revealed by Western blotting analysis that NAC promoted Bcl-2 signaling and decreased p53 signaling. The fndings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an efective part in the regulation of apoptotic markers.