Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Hum Exp Toxicol. 2011 Dec;30(12):1931-44. doi: 10.1177/0960327111402242. Epub 2011 Mar 15.
Although cisplatin is one of the most efficient chemotherapeutic agents for the treatment of solid tumors, frequently observed nephrotoxicity has limited its use in several patients.
The protective effect of Glycine max (GM) and Chrysanthemum indicum (CM) extracts on cisplatin-induced apoptosis in human proximal tubular HK-2 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Hoechst 33342, and propidium iodide assays. Reactive oxygen species (ROS) were determined by flow cytometry with 2,7-dichlorofluorescein diacetate (DCFH(2)-DA).
Cisplatin-induced renal cell toxicity through the induction of hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH(•-)). CM extract protected cisplatin-induced apoptosis by its anti-oxidant activity against H(2)O(2) and OH(•-), while GM extract scavenged only H(2)O(2). Furthermore, GM and CM extracts protect renal cells without significant interfering effect on cisplatin toxicity in lung cancer H460 and melanoma G361 cells.
GM and CM extracts exhibited a promising protective effect on cisplatin-induced nephrotoxicity which could benefit the development for nephroprotective approaches.
虽然顺铂是治疗实体瘤最有效的化疗药物之一，但频繁观察到的肾毒性限制了其在一些患者中的应用。
通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）、Hoechst 33342 和碘化丙啶测定，评估 Glycine max（GM）和 Chrysanthemum indicum（CM）提取物对顺铂诱导的人近端肾小管 HK-2 细胞凋亡的保护作用。通过 2,7-二氯荧光素二乙酸酯（DCFH(2)-DA）用流式细胞术测定活性氧（ROS）。
顺铂通过诱导过氧化氢（H(2)O(2)）和羟基自由基（OH(•-))诱导肾细胞毒性。CM 提取物通过其抗氧化活性对抗 H(2)O(2)和 OH(•-)来保护顺铂诱导的细胞凋亡，而 GM 提取物仅能清除 H(2)O(2)。此外，GM 和 CM 提取物在肺癌 H460 和黑色素瘤 G361 细胞中对顺铂毒性没有明显的干扰作用，保护肾细胞。
GM 和 CM 提取物对顺铂诱导的肾毒性表现出有希望的保护作用，这可能有利于开发肾保护方法。
