Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells
Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells
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马兜铃酸 I 和马兜铃内酰胺 I 对培养肾上皮细胞的毒性
DOI：
10.1016/j.tiv.2010.03.012
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发表时间：
2010-06-01
影响因子：
3.2
通讯作者：
Zhang, Luyong
中科院分区：
文献类型：
--
作者：
Li, Ji;Zhang, Liang;Zhang, Luyong
马兜铃酸肾病是一种进行性肾小管间质性肾病，主要由马兜铃酸 I (AA-I) 中毒引起。马兜铃内酰胺 I (AL-I) 是 AA-I 的主要代谢产物，也可能参与导致肾损伤的过程。为了研究 AL-I 介导的细胞毒性的作用和机制，我们测定并比较了 AA-I 和 AL-I 对人近端肾小管上皮 (HK-2) 细胞系细胞的细胞毒性作用。为此，我们用 AA-I 和 AL-I 处理 HK-2 细胞，并通过使用 3-(4,5-二甲基-噻唑-2-基)-2,5-二苯基-四唑溴化物 (MU) 测定、流式细胞术和测定 caspase 3 活性的测定来评估这些药物的细胞毒性。 HK-2 细胞的增殖以浓度和时间依赖性方式受到抑制。细胞周期分析显示细胞被停滞在 S 期。膜联蛋白 V/碘化丙啶 (PI) 测定结果和亚 G1 峰的出现证明了细胞凋亡。此外，AA-I和AL-I以浓度依赖性方式增加caspase 3样活性。这些结果还表明，AL-I的细胞毒性效力高于AA-I，并且这些分子的细胞毒性作用是通过在caspase 3依赖性途径中诱导细胞凋亡来介导的。 (C) 2010 年，爱思唯尔有限公司出版。
Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is primarily caused by aristolochic acid I (AA-I) intoxication. Aristololactam I (AL-I), the main metabolite of AA-I, may also participate in the processes that lead to renal damage. To investigate the role and mechanism of the AL-I-mediated cytotoxicity, we determined and compared the cytotoxic effects of AA-I and AL-I on cells of the human proximal tubular epithelial (HK-2) cell line. To this end, we treated HK-2 cells with AA-I and AL-I and assessed the cytotoxicity of these agents by using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MU) assay, flow cytometry, and an assay to determine the activity of caspase 3. The proliferation of HK-2 cells was inhibited in a concentration- and time-dependent manner. Cell-cycle analysis revealed that the cells were arrested in the S-phase. Apoptosis was evidenced by the results of the annexin V/propidium iodide (PI) assay and the occurrence of a sub-G1 peak. In addition, AA-I and AL-I increased caspase 3-like activity in a concentration-dependent manner. These results also suggested that the cytotoxic potency of AL-I is higher than that of AA-I and that the cytotoxic effects of these molecules are mediated through the induction of apoptosis in a caspase 3-dependent pathway. (C) 2010 Published by Elsevier Ltd.