Nho Jong-Hyun, Jung Ho-Kyung, Lee Mu-Jin, Jang Ji-Hun, Sim Mi-Ok, Jeong Da-Eun, Cho Hyun-Woo, Kim Jong-Choon
National Development Institute of Korean Medicine, Jangheung, Korea.
College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
Toxicol Res. 2018 Apr;34(2):133-141. doi: 10.5487/TR.2018.34.2.133. Epub 2018 Apr 15.
Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury , we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury and , and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.
顺铂和阿霉素等抗癌药物的使用效果比放射疗法更好。顺铂是一种化疗药物，用于治疗各种癌症。然而，它具有耳毒性和肾毒性等副作用。顺铂诱导的肾毒性会增加肾小管损伤和肾功能障碍。因此，我们使用HK-2细胞（人近端肾小管细胞系）和动物模型研究了矢车菊苷对顺铂诱导的肾损伤的有益作用。结果表明，10μM矢车菊苷可减少顺铂诱导的细胞凋亡、线粒体功能障碍和半胱天冬酶-3激活，HK-2细胞中经矢车菊苷处理后，顺铂诱导的半胱天冬酶-3/MST-1途径上调有所降低。为了证实矢车菊苷对顺铂诱导的肾损伤的作用，我们使用了顺铂暴露动物模型（20mg/kg，balb/c小鼠，腹腔注射，每天一次，共3天）。矢车菊苷（10mg/kg，腹腔注射，每天一次，共3天）可降低顺铂注射诱导的肾功能障碍、肾小管损伤和中性粒细胞增多。结果表明，矢车菊苷可减轻顺铂诱导的肾损伤，可用于改善顺铂诱导的副作用。然而，关于高剂量矢车菊苷的毒性以及动物模型中半胱天冬酶-3/MST-1相关信号转导，还需要进一步的实验。
