Yang Suwen, Wang Shengrui, Sun Fengchao, Zhang Mengmeng, Wu Fengchang, Xu Fanfan, Ding Zhishan
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.
Department of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Environ Toxicol. 2015 Sep;30(9):1014-23. doi: 10.1002/tox.21975. Epub 2014 Mar 5.
Tetrabromobisphenol A (TBBPA), a brominated flame retardant, is detected commonly in aquatic environments, where it is thought to be highly toxic to the development of aquatic life. In this study, zebrafish embryos and larvae were used to investigate the protective effects of puerarin after exposure to TBBPA. Malformation, blood flow disorders, pericardial edema, and spawn coagulation rates increased, whereas survival decreased significantly after exposure to 0.5 and 1.0 mg L(-1) TBBPA. The measured indices of morphological toxicity improved after treatment with puerarin. TBBPA also induced reactive oxygen species (ROS) production in a dose-dependent manner. Acridine orange staining results revealed that TBBPA exposure caused cardiomyocyte apoptosis and induced the expression of three proapoptotic genes: P53, Bax, and Caspase9. In contrast, the expression of the antiapoptotic gene Bcl2 was down-regulated. When genes related to cardiac development were assessed, the expression of Tbx1, Raldh2, and Bmp2b changed after exposure to the combination of TBBPA and puerarin. These results suggest that TBBPA induces cardiomyocyte apoptosis and ROS production, resulting in cardiac developmental toxicity in zebrafish embryos or larvae. Therefore, puerarin regulates the expression of cardiac developmental genes, such as Tbx1, Bmp2b, and Raldh2 by inhibiting ROS production, and subsequently modulates cardiac development after the exposure of zebrafish larvae to TBBPA.
四溴双酚A（TBBPA）是一种溴化阻燃剂，在水生环境中普遍被检测到，据认为它对水生生物的发育具有高毒性。在本研究中，使用斑马鱼胚胎和幼体来研究葛根素在暴露于TBBPA后的保护作用。暴露于0.5和1.0 mg L(-1)的TBBPA后，畸形、血流紊乱、心包水肿和产卵凝结率增加，而存活率显著下降。用葛根素处理后，所测形态毒性指标有所改善。TBBPA还以剂量依赖的方式诱导活性氧（ROS）的产生。吖啶橙染色结果显示，暴露于TBBPA会导致心肌细胞凋亡，并诱导三个促凋亡基因P53、Bax和Caspase9的表达。相反，抗凋亡基因Bcl2的表达下调。当评估与心脏发育相关的基因时，暴露于TBBPA和葛根素的组合后，Tbx1、Raldh2和Bmp2b的表达发生了变化。这些结果表明，TBBPA诱导心肌细胞凋亡和ROS产生，导致斑马鱼胚胎或幼体出现心脏发育毒性。因此，葛根素通过抑制ROS的产生来调节心脏发育基因如Tbx1、Bmp2b和Raldh2的表达，随后在斑马鱼幼体暴露于TBBPA后调节心脏发育。
