A systematic comparison of the developmental vascular toxicity of bisphenol A and its alternatives in vivo and in vitro
A systematic comparison of the developmental vascular toxicity of bisphenol A and its alternatives in vivo and in vitro
复制标题
双酚 A 及其替代品体内外发育血管毒性的系统比较。
DOI：
10.1016/j.chemosphere.2021.132936
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发表时间：
2022-01-19
期刊：
影响因子：
8.8
通讯作者：
Gu, Aihua
中科院分区：
文献类型：
--
作者：
Ji, Guixiang;Gu, Jie;Gu, Aihua
由于双酚A的潜在毒性，双酚F、双酚S和双酚AF等几种双酚已逐渐被用作其主要替代品，并且这些替代品在不同环境介质中的水平不断上升。尽管先前的一些研究表明，双酚替代品具有与双酚A相似或更大的急性毒性和雌激素样作用，但关于双酚的心血管毒性的比较研究尚未得到评估。本研究利用斑马鱼胚胎和人血管内皮细胞(HUVECs)评价了BPA及其三种主要替代物(BPF、BPS和BPAF)的血管发育毒性。1/10 96h半致死浓度(96HLC(50))的BP暴露显著抑制了TG(FLI1：EGFP)斑马鱼胚胎节段间血管(ISV)的生长，延缓了主总静脉(CCV)的重建，并减少了肠下血管(SIV)。同时，内皮管形成实验结果显示，BP可抑制体外血管生成。从机制上讲，BP暴露增加了氧化应激，其特征是斑马鱼和HUVECs中的超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性显著下降，同时丙二醛(MDA)和活性氧(ROS)水平上升。因此，对BPS的血管毒性和氧化应激能力进行了比较和评价，其顺序为：BPAF>；BPF>；BPA>；BPS。据我们所知，本工作首次系统地为双酚A及其替代品在体外和体内发育血管毒性方面提供了直接证据。因此，这些发现将为双酚A替代品的合理和安全应用提供洞察力。
Due to the potential toxicity of bisphenol A (BPA), several bisphenols (BPs), including bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF), have been gradually used as its main substitutes, and the levels of these alternatives in different environmental media have been constantly increasing. Although some previous studies have shown that bisphenol substitutes have similar or greater acute toxicity and estrogenic effects than BPA, comparative studies on the cardiovascular toxicity of BPs have not been evaluated. In this study, the developmental vascular toxicity of BPA and three predominant substitutes (BPF, BPS and BPAF) were evaluated using zebrafish embryos and human vascular endothelial cells (HUVECs). BP exposure at a sublethal concentration of 1/10 96 h median lethal concentration (96 hLC(50)) significantly hindered intersegmental vessel (ISV) growth, delayed common cardinal vein (CCV) remodeling and decreased subintestinal vessels (SIVs) in Tg (fli1:EGFP) zebrafish embryos. Meanwhile, the results of the endothelial tube formation assay showed that in vitro angiogenesis was inhibited by BP exposure. Mechanistically, BP exposure increased oxidative stress characterized by a significant decrease in superoxide dismutase (SOD) and catalase (CAT) activity, accompanied by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in both zebrafish and HUVECs. Therefore, the vascular toxicity and oxidative stress potency of the BPs were compared and evaluated, ranking as follows: BPAF > BPF > BPA > BPS. To the best of our knowledge, the present work, for the first time, systematically provides direct evidence for BPA and its alternatives on developmental vascular toxicity in vitro and in vivo. Therefore, these findings will provide insight into the rational and safe application of BPA substitutes.