Zoology Department, Faculty of Science, Suez University, Suez, 43533, Egypt.
Chemistry Department, Faculty of Science, Suez University, Suez, 43533, Egypt.
Sci Rep. 2022 Nov 19;12(1):19903. doi: 10.1038/s41598-022-21681-8.
The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMCS against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMCS has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.
顺铂（CDDP）对肾小管的毒性及其对近端肾小管的严重影响限制了其在癌症治疗中的进一步应用。本研究旨在评估没食子酸接枝 O-羧甲基壳聚糖（GA@CMCS）对顺铂诱导的大鼠肾毒性的保护作用。通过肾损伤分子-1（KIM-1）评估 GA@CMCS/CDDP 处理大鼠的肾损伤。此外，还测量了还原型谷胱甘肽（GSH）、丙二醛（MDA）和一氧化氮（NO）的水平。彗星试验用于测量 DNA 损伤。GA@CMCS 的肾保护活性得到了肾组织病理和免疫病理学研究的支持。GA@CMCS 可显著使 CDDP 诱导的肾匀浆中 KIM-1、MDA 和 NO 升高正常化，与 CDDP 组相比，GSH 显著增加。GA@CMCS 还可显著防止大鼠肾脏发生 CDDP 诱导的组织病理和免疫病理学变化。生化发现和组织病理及免疫病理学证据均表明，GA@CMCS 具有减轻 CDDP 诱导的氧化应激、炎症和肾功能障碍的肾保护作用。总之，GA@CMCS 已被证明可减轻癌症治疗中 CDDP 的肾毒性影响。
