Lee Jinkyung, Nguyen Quynh Nhu, Park Jun Yeon, Lee Sullim, Hwang Gwi Seo, Yamabe Noriko, Choi Sungyoul, Kang Ki Sung
College of Korean Medicine, Gachon University, Seongnam 13120, Korea.
Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Korea.
Plants (Basel). 2020 Dec 1;9(12):1681. doi: 10.3390/plants9121681.
Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of extract and its mechanism of action against cisplatin-induced renal injury.
肾毒性是顺铂的一种严重副作用,顺铂是癌症治疗中最常用的药物之一。本研究旨在评估提取物及其生物活性化合物(莽草酸)对顺铂诱导的肾损伤的肾脏保护作用。在肾小管上皮细胞(LLC-PK1)中进行体外试验,使用50、100和200 µg/mL的提取物以及25和50 µM的莽草酸,并用25 µM顺铂诱导细胞毒性。对6周龄的BALB/c小鼠一次性注射16 mg/kg顺铂,并每天口服25和50 mg/kg的莽草酸,持续4天。结果表明,提取物逆转了顺铂诱导的肾细胞活力下降,同时降低了LLC-PK1细胞中活性氧化应激的积累和细胞凋亡。与顺铂处理组相比,莽草酸也逆转了对细胞活力的影响,但降低了肾细胞中的氧化应激和细胞凋亡。此外,莽草酸通过降低血清肌酐水平对顺铂处理的小鼠起到肾脏保护作用。顺铂处理的小鼠肾脏组织学损伤的恢复证实了莽草酸对顺铂介导的肾脏损伤的保护作用。据我们所知,本研究是关于提取物对顺铂诱导的肾损伤的肾脏保护作用及其作用机制的首次报道。