期刊
CHEMOSPHERE
卷 286, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2021.131550
关键词
Decabromodiphenyl ethane; Oxidative stress; Endoplasmic reticulum stress; CYP3A; Hepatotoxicity
资金
- National Natural Science Foundation of China [21777107, 21477083]
DBDPE exposure induces toxic effects on hepatocytes by causing oxidative stress and endoplasmic reticulum stress, leading to cell damage and apoptosis. In addition, DBDPE exposure also decreases CYP3A expression levels.
Decabromodiphenyl ethane (DBDPE) is one of the most commonly used novel brominated flame retardants (NBFRs), and its mass production and widespread application have caused health threats to the human being. Existing studies have shown that DBDPE has hepatotoxicity. And we have found that DBDPE could change cytochrome P450 3A (CYP3A) expression levels in rat livers, whereas the mechanism is unclear. In this study, we exposed human normal hepatocyte (L-02) to DBDPE to further study the effect and mechanism of DBDPE on hepatocellular injury and liver metabolic enzyme CYP3A changes in vitro. The results showed that DBDPE caused L-02 cell viability decrease, lactate dehydrogenase (LDH) and transaminase release, ultrastructural damage, and apoptosis. Moreover, DBDPE exposure induced oxidative stress (i.e., increased ROS generation and MDA levels and decreased GSH content, SOD activity, and mitochondrial membrane potential) and endoplasmic reticulum (ER) stress in L-02 cells as evidenced by the elevated PERK and IRE-1 alpha expression levels. These results confirmed that DBDPE is toxic to hepatocytes. Besides, the CYP3A expression level was decreased in DBDPE exposed L-02 cells. However, pretreatment of L-02 cells with antioxidant N-Acetyl-L-cysteine (NAC) and endoplasmic reticulum stress inhibitor 4-PBA inhibited DBDPE-induced oxidative stress, endoplasmic reticulum stress, CYP3A expression decrease, and apoptosis. Therefore, we demonstrated that DBDPE could exert toxic effects and decrease CYP3A expression on L-02 cells by inducing ER stress and oxidative stress.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据