Protective effect of green tea extract and tea polyphenols against FK506-induced cytotoxicity in renal cells
Protective effect of green tea extract and tea polyphenols against FK506-induced cytotoxicity in renal cells
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DOI：
10.1111/j.1742-7843.2006.pto_284.x
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发表时间：
2006-02-01
影响因子：
3.1
通讯作者：
Matsui-Yuasa, I
中科院分区：
文献类型：
--
作者：
Hisamura, F;Kojima-Yuasa, A;Matsui-Yuasa, I
免疫抑制药物FK 506（他克莫司或藤霉素）诱导的肾毒性限制了其广泛应用的有效性，其潜在机制尚未完全了解。FK 506在肾脏中的主要靶点是近端肾小管上皮细胞。在这项研究中，研究了绿色茶提取物对FK 506诱导的LLC-PK 1细胞死亡的保护作用。FK 506导致细胞存活率显著降低，但添加绿色茶提取物以剂量依赖性方式降低了这种效应。用50 μ M处理细胞（41.1 μ g/ml）FK 506诱导膜联蛋白V阳性/碘化丙啶阴性细胞从2.68%显著增加至14.5%，而添加6.25、12.5和25 μ g/ml的绿色茶提取物导致凋亡细胞从14.5%显著增加至6.51%，分别为3.20和3.02%。还研究了五种不同成分的茶多酚的效果。表没食子儿茶素没食子酸酯和表没食子儿茶素显着降低FK 506诱导的细胞毒性，但表儿茶素和儿茶素对细胞活力没有影响。此外，还研究了细胞色素c释放和半胱天冬酶激活（细胞凋亡的特征）的变化。表没食子儿茶素没食子酸酯和表没食子儿茶素抑制FK 506处理的LLC-PK 1细胞中细胞色素c的显著释放和caspase-3的活化。
The nephrotoxicity induced by the immunosuppressive drug FK506 (tacrolimus or fujimycin), limits its usefulness in widespread application, and the underlying mechanism has not been completely understood. The primary targets of FK506 in the kidney are the proximal tubular epithelial cells. In this study, the protection of green tea extract against FK506-induced cell death of LLC-PK1 cells was investigated. FK506 caused a significant decrease in survival of the cells, but the addition of green tea extract reduced this effect in a dose-dependent manner. Treatment of the cells with 50 mu M (41.1 mu g/ml) FK506 induced a significant increase in annexin V-positive/propidium iodide-negative cells from 2.68 to 14.5%, whereas the addition of 6.25, 12.5, and 25 mu g/ml of green tea extract caused a significant protective effect in apoptotic cells from 14.5 to 6.51, 3.20 and 3.02%, respectively. The effect of five different constituent tea polyphenols was also examined. Epigallocatechin-gallate and epigallocatechin significantly reduced FK506-induced cytotoxicity but epicatechin and catechin had no effect on cell viability. Furthermore, changes in cytochrome c release and caspase activation, which characterize apoptosis, were studied. Epigallocatechin-gallate and epigallocatechin suppressed a significant release of cytochrome c and activation of caspase-3 in FK506-treated LLC-PK1 cells.