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Silymarin selectively protects human renal cells from cisplatin-induced cell death.

机译:水飞蓟素选择性保护人肾细胞免受顺铂诱导的细胞死亡。

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CONTEXT: Cisplatin-induced nephrotoxicity has been accepted as an important obstacle for efficient cisplatin-based chemotherapy. Silymarin from seeds of milk thistle [Silybum marianum L. (Asteraceae)] has been shown to possess various potential pharmacological properties; however, whether or not this agent selectively protects renal cells from cisplatin-induced cell death with no interfering effect on cancer cells is not clear. OBJECTIVE: Potential of silymarin in protection of cisplatin-induced renal cell death without compromising effect on anticancer activity of cisplatin was demonstrated in this study. MATERIALS AND METHODS: Cisplatin-induced cell death was evaluated in human proximal tubular HK-2, lung carcinoma H460, and melanoma G361 cells using MTT, Hoechst 33342, and propidium iodide assays. RESULTS: Cisplatin induced both apoptosis and necrosis in HK-2 cells and caused a decrease in cell viability by ~40% and 60% at the doses of 25 and 100 microM, respectively. Pretreatment with 25-200 microM of silymarin significantly protected against cisplatin-induced cell death in a dose-dependent manner. In contrast, pretreatment of silymarin (25-100 microM) caused no significant change on cisplatin-induced cell death in H460 cells but significantly potentiated cisplatin-induced apoptosis in G361 cells. DISCUSSION AND CONCLUSION: These findings reveal the selectivity of silymarin in protection of renal cells from cisplatin-induced cell death and could be beneficial for the development of this considerately safe compound as a renoprotective agent.
机译:背景:顺铂诱导的肾毒性已被认为是有效的基于顺铂的化学治疗的重要障碍。水飞蓟籽[水飞蓟]的水飞蓟素已显示出具有多种潜在的药理特性。然而,尚不清楚该药物是否选择性地保护肾细胞免受顺铂诱导的细胞死亡而对癌细胞没有干扰作用。目的:水飞蓟素在保护顺铂诱导的肾细胞死亡而不损害顺铂抗癌活性的作用中具有潜力。材料与方法:使用MTT,Hoechst 33342和碘化丙锭测定法评估了人近端肾小管HK-2,肺癌H460和黑色素瘤G361细胞中顺铂诱导的细胞死亡。结果:顺铂诱导HK-2细胞凋亡和坏死,并在25和100 microM剂量下分别导致细胞活力降低约40%和60%。用25-200 microM水飞蓟素进行预处理,可以剂量依赖性方式显着保护顺铂诱导的细胞死亡。相反,水飞蓟素(25-100 microM)的预处理在H460细胞中对顺铂诱导的细胞死亡没有造成明显变化,但在G361细胞中显着增强了顺铂诱导的细胞凋亡。讨论与结论:这些发现揭示了水飞蓟素在保护肾细胞免受顺铂诱导的细胞死亡中的选择性,并且可能有益于开发这种作为肾脏保护剂的相当安全的化合物。

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