Pang Yaqin, Qi Guangzi, Jiang Sili, Zhou Ying, Li Wenxue
a Youjiang Medical University for Nationalities, Faculty of Toxicology, School of Public Health, Baise, Guangxi, China.
b Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, China.
Can J Physiol Pharmacol. 2018 Nov;96(11):1119-1126. doi: 10.1139/cjpp-2017-0677. Epub 2018 May 31.
1,2-Dichloroethane (DCE) is a ubiquitous occupational environmental contaminant. Subacute exposure to DCE can cause severe toxic encephalopathy and has obvious toxic effects on the liver. However, the toxicity of DCE on the liver and its molecular mechanism remain elusive. In the present study, we established a DCE-exposed animal model by inhalation in SD rats and used HepG2 cells in in vitro tests. The DCE-exposed groups showed hepatic dysfunction relative to the control group. Moreover, apoptotic cells and decreased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) were found in liver tissue of rats in 3 DCE-exposed groups. In vitro tests showed that short-term exposure to DCE induced apoptosis in HepG2 cells. Furthermore, the incubation of cells with DCE significantly decreased the phosphorylation of ERK1/2 in a concentration-dependent manner. Additionally, incubating HepG2 cells with epidermal growth factor, an ERK1/2 activator, significantly increased apoptosis in HepG2 cells. In conclusion, our results suggest that DCE induces apoptosis in HepG2 cells by inhibiting ERK1/2 pathways.
1,2 - 二氯乙烷（DCE）是一种普遍存在的职业环境污染物。亚急性接触DCE可导致严重的中毒性脑病，并对肝脏有明显的毒性作用。然而，DCE对肝脏的毒性及其分子机制仍不清楚。在本研究中，我们通过吸入法在SD大鼠中建立了DCE暴露动物模型，并在体外试验中使用了HepG2细胞。与对照组相比，DCE暴露组表现出肝功能障碍。此外，在3个DCE暴露组大鼠的肝脏组织中发现了凋亡细胞以及细胞外信号调节激酶1/2（ERK1/2）磷酸化水平降低。体外试验表明，短期接触DCE可诱导HepG2细胞凋亡。此外，用DCE孵育细胞以浓度依赖性方式显著降低了ERK1/2的磷酸化水平。另外，用ERK1/2激活剂表皮生长因子孵育HepG2细胞可显著增加HepG2细胞的凋亡。总之，我们的结果表明，DCE通过抑制ERK1/2途径诱导HepG2细胞凋亡。
