State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Institute for Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
Chemosphere. 2019 Jul;226:463-471. doi: 10.1016/j.chemosphere.2019.03.167. Epub 2019 Mar 29.
Tetrabromobisphenol A (TBBPA) is a commonly used brominated flame retardant, which has a wide range of toxic effects on organisms. This study investigated the cytotoxic effects on human hepatocytes (L02 cells) after treated with 0, 5, 10, 20, and 40 μM of TBBPA. Results showed that TBBPA significantly increased intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and the ratio of oxidized/reduced glutathione (GSSG/GSH) dose-dependently. TBBPA also decreased the cell mitochondrial membrane potential (MMP), caused the release of cytochrome C (Cyt C) to cytoplasm and promoted the expression of caspase-9 and caspase-3, and finally increased the level of apoptosis. The ROS inhibitor N-acetyl-L-cysteine (NAC) relieved the oxidative stress responses, and prevented the decrease of MMP and increase of apoptosis. In addition, TBBPA promoted the expression of antioxidant genes related to Nrf2, such as quinone oxidoreductase 1 (NQO1), catalase (CAT), and heme oxygenase 1 (HO-1). Oxidative stress initiated by TBBPA, activated mitochondrial apoptosis and Nrf2 pathway, and increased the degree of apoptosis in L02 cells.
四溴双酚 A（TBBPA）是一种常用的溴系阻燃剂，对生物体具有广泛的毒性作用。本研究探讨了不同浓度（0、5、10、20 和 40μM）的 TBBPA 处理人肝细胞（L02 细胞）后的细胞毒性作用。结果表明，TBBPA 可显著增加细胞内活性氧（ROS）、丙二醛（MDA）和氧化型/还原型谷胱甘肽（GSSG/GSH）的比值，呈剂量依赖性。TBBPA 还降低了线粒体膜电位（MMP），导致细胞色素 C（Cyt C）释放到细胞质中，并促进了胱天蛋白酶-9 和胱天蛋白酶-3 的表达，最终增加了细胞凋亡水平。ROS 抑制剂 N-乙酰-L-半胱氨酸（NAC）缓解了氧化应激反应，并防止了 MMP 的降低和凋亡的增加。此外，TBBPA 还促进了与 Nrf2 相关的抗氧化基因的表达，如醌氧化还原酶 1（NQO1）、过氧化氢酶（CAT）和血红素加氧酶 1（HO-1）。TBBPA 引发的氧化应激激活了线粒体凋亡和 Nrf2 通路，增加了 L02 细胞的凋亡程度。
