Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells
Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells
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姜黄素通过相反调节人肝细胞 L02 细胞中的 Nrf2/HO-1 和 NF-kB 通路来减轻喹烯酮诱导的细胞凋亡和炎症
DOI：
10.1016/j.fct.2016.06.025
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发表时间：
2016-09-01
影响因子：
4.3
通讯作者：
Tang, Shusheng
中科院分区：
文献类型：
--
作者：
Dai, Chongshan;Li, Bin;Tang, Shusheng
喹烯酮（QCT）的潜在毒性引起了广泛关注，但其机制仍不清楚。本研究旨在探讨姜黄素对QCT诱导的人肝细胞L02细胞凋亡的保护作用及其潜在机制。结果表明，QCT处理显着降低了L02细胞的细胞活力，增加了乳酸脱氢酶（LDH）的释放，姜黄素预处理在1.25、2.5和5 M时减弱了这种作用。与单独QCT组相比，姜黄素预处理显着减弱了QCT诱导的氧化应激、线粒体功能障碍和细胞凋亡。此外，姜黄素预处理以剂量依赖性方式显着减弱 QCT 诱导的 iNOS 活性和 NO 产生的增加。同时，与单独QCT组相比，姜黄素预处理显着下调核因子kB（NF-kB）和iNOS mRNA的表达，但上调Nrf2和HO-1 mRNA的表达。锌原卟啉 IX 是一种 HO-1 抑制剂，可部分显着消除姜黄素对 QCT 诱导的 caspase 激活和 NF-kB mRNA 表达的细胞保护作用。这些结果表明姜黄素能有效抑制QCT诱导的L02细胞凋亡和炎症反应，其机制可能与Nrf2/HO-1的激活和NF-kB通路的抑制有关。(C) 2016 Elsevier Ltd. 版权所有。
The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 M. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.(C) 2016 Elsevier Ltd. All rights reserved.