School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072, China; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072, China.
Sci Total Environ. 2024 May 20;926:172000. doi: 10.1016/j.scitotenv.2024.172000. Epub 2024 Mar 27.
Perfluoroalkyl acids (PFAAs) of different chemical speciation were previously found to cause diverse toxicity. However, the toxicological mechanisms depending on chemical speciation are still largely unknown. In this follow-up study, zebrafish embryos were acutely exposed to only one concentration at 4.67 μM of the acid and salt of representative PFAAs, including perfluorooctanoic acid (PFOA), perfluorobutane carboxylic acid (PFBA), and perfluorobutanesulfonic acid (PFBS), till 96 h post-fertilization (hpf), aiming to gain more mechanistic insights. High-throughput proteomics found that PFAA acid and salt exerted discriminative effects on protein expression pattern. Bioinformatic analyses based on differentially expressed proteins underlined the developmental cardiotoxicity of PFOA acid with regard to cardiac muscle contraction, vascular smooth muscle contraction, adrenergic signaling in cardiomyocytes, and multiple terms related to myocardial contraction. PFOA salt and PFBS acid merely disrupted the cardiac muscle contraction pathway, while cardiac muscle cell differentiation was significantly enriched in PFBA acid-exposed zebrafish larvae. Consistently, under PFAA exposure, especially PFOA and PFBS acid forms, transcriptional levels of key genes for cardiogenesis and the concentrations of troponin and epinephrine associated with myocardial contraction were significantly dysregulated. Moreover, a transgenic line Tg (my17: GFP) expressing green fluorescent protein in myocardial cells was employed to visualize the histopathology of developing heart. PFOA acid concurrently caused multiple deficits in heart morphogenesis and function, which were characterized by the significant increase in sinus venosus and bulbus arteriosus distance (SV-BA distance), the induction of pericardial edema, and the decrease in heart rate, further confirming the stronger toxicity of PFOA acid than the salt counterpart on heart development. Overall, this study highlighted the developmental cardiotoxicity of PFAAs, with potency ranking PFOA > PFBS > PFBA. The acid forms of PFAAs induced stronger cardiac toxicity than their salt counterparts, providing an additional insight into the structure-toxicity relationship.
全氟烷基酸（PFAAs）具有不同的化学形态，先前被发现会引起多种毒性。然而，取决于化学形态的毒理学机制在很大程度上仍然未知。在这项后续研究中，我们将斑马鱼胚胎急性暴露于仅一种浓度（4.67 μM）的代表性 PFAAs 的酸和盐，包括全氟辛酸（PFOA）、全氟丁烷羧酸（PFBA）和全氟丁烷磺酸（PFBS），直到受精后 96 小时（hpf），旨在获得更多的机制见解。高通量蛋白质组学发现，PFAAs 的酸和盐对蛋白质表达模式产生了有区别的影响。基于差异表达蛋白的生物信息学分析强调了 PFOA 酸对心脏肌肉收缩、血管平滑肌收缩、心肌细胞中的肾上腺素能信号以及与心肌收缩相关的多个术语的发育性心脏毒性。PFOA 盐和 PFBS 酸仅破坏了心脏肌肉收缩途径，而 PFBA 酸暴露的斑马鱼幼虫中明显富集了心肌细胞分化。一致地，在 PFAAs 暴露下，特别是 PFOA 和 PFBS 酸形式，心脏发生的关键基因的转录水平以及与心肌收缩相关的肌钙蛋白和肾上腺素的浓度显著失调。此外，使用表达心肌细胞中绿色荧光蛋白的转基因系 Tg(my17: GFP)来可视化正在发育的心脏的组织病理学。PFOA 酸同时导致心脏形态发生和功能的多种缺陷，其特征是窦房静脉和动脉球距离（SV-BA 距离）显著增加、心包水肿的诱导以及心率降低，进一步证实了 PFOA 酸对心脏发育的毒性强于其盐对应物。总的来说，这项研究强调了 PFAAs 的发育性心脏毒性，其效力等级为 PFOA > PFBS > PFBA。PFAAs 的酸形式比其盐形式引起更强的心脏毒性，为结构-毒性关系提供了额外的见解。
