Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China.
Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Sci Total Environ. 2020 Aug 20;731:139190. doi: 10.1016/j.scitotenv.2020.139190. Epub 2020 May 4.
Research has shown that there is a relationship between bisphenol A (BPA) exposure and the incidence of cardiovascular diseases. However, the effect of bisphenol AF (BPAF), a main substitute for BPA, on heart development remains unclear. In this study, the cardiotoxicity of BPAF was evaluated in zebrafish in vivo and in human cardiac myocytes (HCMs) in vitro. Our results showed that BPAF at a concentration of 200 μg/L results in cardiotoxicity, including a reduced number of cardiomyocytes and endocardial cells in the heart, and reduced heart size in two transgenic zebrafish models (myl7:: dsred2-nuc and fli1a::nGFP). An increase in apoptosis was observed along with antioxidant enzyme inhibition and lipid peroxidation. In addition, the mRNA expression levels of several key genes involved in cardiac development were suppressed by BPAF treatment. In the HCM cell model, BPAF at 2 mg/L induced reactive oxygen species generation, antioxidant enzyme inhibition, mitochondrial dysfunction and oxidative DNA damage. These adverse outcomes can be attenuated by the antioxidant N-acetyl-L-cysteine (NAC), suggesting that oxidative stress is involved in BPAF-induced cardiotoxicity. These data indicated that BPAF exposure increased oxidative stress and apoptosis and that it suppressed the expression of genes involved in cardiac development, which may play crucial roles in the mechanisms of BPAF-induced cardiotoxicity.
研究表明，双酚 A（BPA）暴露与心血管疾病的发病率之间存在关联。然而，BPA 的主要替代品双酚 AF（BPAF）对心脏发育的影响尚不清楚。在这项研究中，我们在体内斑马鱼和体外人心肌细胞（HCM）中评估了 BPAF 的心脏毒性。结果表明，浓度为 200μg/L 的 BPAF 具有心脏毒性，包括两种转基因斑马鱼模型（myl7::dsred2-nuc 和 fli1a::nGFP）中心肌细胞和心内膜细胞数量减少，心脏缩小。抗氧化酶抑制和脂质过氧化伴随着细胞凋亡增加。此外，BPAF 处理还抑制了几个参与心脏发育的关键基因的 mRNA 表达水平。在 HCM 细胞模型中，2mg/L 的 BPAF 诱导活性氧生成、抗氧化酶抑制、线粒体功能障碍和氧化 DNA 损伤。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）可以减轻这些不良后果，表明氧化应激参与了 BPAF 诱导的心脏毒性。这些数据表明，BPAF 暴露增加了氧化应激和细胞凋亡，并抑制了心脏发育相关基因的表达，这可能在 BPAF 诱导的心脏毒性机制中发挥关键作用。
