Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.
Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.
复制标题
DOI：
10.1371/journal.pone.0113257
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ren H
中科院分区：
文献类型：
--
作者：
Jin X;Song L;Liu X;Chen M;Li Z;Cheng L;Ren H
二氯二苯氧三氯乙烷（DDT）是一种已知的持久性有机污染物和肝损伤毒物。然而，关于DDT的肝损伤毒性及其有效抑制剂的机制却鲜有关注。因此，本研究旨在探讨维生素C （VC）和维生素E （VE）对DDT对HL-7702细胞毒性的保护作用，并阐述其具体的分子机制。结果表明，p，p′-DDT暴露在10µM以上，可使HL-7702细胞活力下降，导致细胞凋亡。p,p ' -DDT处理提高活性氧（ROS）生成水平，诱导线粒体膜电位，并将细胞色素c释放到细胞质中，随后Bax和p53升高，同时抑制Bcl-2。此外，caspase-3和-8也被激活。p、p′-DDT能促进NF-κB和FasL的表达。当细胞暴露于NF-κB抑制剂（PDTC）时，FasL的上调表达减弱。引人注目的是，这些由DDT处理引起的改变可以通过添加VC或VE来预防或逆转，并且VC和VE共同处理的保护作用高于单独添加p，p ' -DDT。综上所述，这些发现提供了新的实验证据，支持VC或/和VE可以通过ros介导的线粒体途径和NF-κB/FasL途径降低p，p ' - ddt诱导的HL-7702细胞毒性。
Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p′-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p′-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p′-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p′-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p′-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.
登录
查看更多内容
影响因子：
3.8
作者：
Feng, Gong;Li, Ying;Bai, Yansheng
通讯作者：
Bai, Yansheng
影响因子：
--
作者：
Aziz R;Rafiq MT;Yang J;Liu D;Lu L;He Z;Daud MK;Li T;Yang X
通讯作者：
Yang X
影响因子：
11.2
作者：
Heaney ML;Gardner JR;Karasavvas N;Golde DW;Scheinberg DA;Smith EA;O'Connor OA
通讯作者：
O'Connor OA
影响因子：
3.8
作者：
Jaeschke, H;Gores, GJ;Lemasters, JJ
通讯作者：
Lemasters, JJ
影响因子：
4.5
作者：
Durak, Dilek;Uzun, Fatma Goekce;Kalender, Yusuf
通讯作者：
Kalender, Yusuf