Faculty of Medicine, Department of Biophysics, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.
Faculty of Medicine, Department of Histology-Embryology, İzmir Democracy University, İzmir, Turkey.
Mol Biol Rep. 2021 Jan;48(1):637-644. doi: 10.1007/s11033-020-06111-0. Epub 2021 Jan 13.
CP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic effects. The present study aimed to reveal the effects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological findings. 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 significant 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 CP-induced inflammation 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 findings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an effective part in the regulation of apoptotic markers.
CP 是最广泛使用的抗肿瘤药物之一。然而，由于其严重的毒性作用，其临床应用非常有限。本研究旨在揭示 NAC 的作用，NAC 在减轻 CP 引起的肝损伤方面具有广泛的生物学活性，同时考虑到生化、遗传和组织病理学发现。将 28 只 Wistar 大鼠随机分为四组，每组 7 只。对照组给予生理盐水（i.p.）5 天，NAC 组给予 NAC（200mg/kg）5 天（i.p.）。CP 组在实验的第 2 天和第 5 天给予 CP（7.5mg/kg），实验的第 5 天给予 NAC（200mg/kg）（i.p.）。CP 组在实验的第 2 天和第 5 天给予 CP（7.5mg/kg）。实验结束时，对所有大鼠分离的肝组织进行生化、组织学和 mRNA 表达分析。与对照组和 CP 组相比，NAC+CP 组的 AST 和 ALT 酶活性明显下降。此外，研究还发现，NAC 通过增加 NF-κB 水平，减少 CP 引起的炎症，同时通过降低 GPx 水平，减少 CP 引起的氧化应激。此外，组织病理学分析显示，NAC 改善了肝脏形态。Western blot 分析显示，NAC 促进了 Bcl-2 信号通路，减少了 p53 信号通路。研究结果表明，NAC 通过减少 CP 引起的氧化应激，在调节凋亡标志物方面发挥有效作用，从而有助于减轻严重的治疗并发症肝毒性。
