Sun Sujie, Li Xue, Zhang Li, Zhong Zilin, Chen Chao, Zuo Yuhua, Chen Yu, Hu Hongmei, Liu Fasheng, Xiong Guanghua, Lu Huiqiang, Chen Jianjun, Dai Jiayin
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.
Sci Total Environ. 2023 Feb 10;859(Pt 1):160087. doi: 10.1016/j.scitotenv.2022.160087. Epub 2022 Nov 11.
Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has emerged as a potential environmental pollutant. Here, to investigate the toxic effects of HFPO-TA on liver and biliary system development, zebrafish embryos were exposed to 0, 50, 100, or 200 mg/L HFPO-TA from 6 to 120 h post-fertilization (hpf). Results showed that the 50 % lethal concentration (LC) of HFPO-TA was 231 mg/L at 120 hpf, lower than that of PFOA. HFPO-TA exposure decreased embryonic hatching, survival, and body length. Furthermore, HFPO-TA exerted higher toxicity at the specification stage than during the differentiation and maturation stages, leading to small-sized livers in Tg(fabp10a: DsRed) transgenic larvae and histopathological changes. Significant decreases in the mRNA expression of genes related to liver formation were observed. Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) levels were significantly increased. HFPO-TA decreased total cholesterol (TCHO) and triglyceride (TG) activities, disturbed lipid metabolism through the peroxisome proliferator-activated receptor (PPAR) pathway, and induced an inflammatory response. Furthermore, HFPO-TA inhibited intrahepatic biliary development in Tg(Tp1:eGFP) transgenic larvae and interfered with transcription of genes associated with biliary duct development. HFPO-TA reduced bile acid synthesis but increased bile acid transport, resulting in disruption of bile acid metabolism. Therefore, HFPO-TA influenced embryonic liver and biliary system morphogenesis, caused liver injury, and may be an unsafe alternative for PFOA.
六氟环氧丙烷三聚体酸（HFPO-TA）作为全氟辛酸（PFOA）的一种新型替代品，已成为一种潜在的环境污染物。在此，为了研究HFPO-TA对肝脏和胆道系统发育的毒性作用，在受精后6至120小时（hpf）将斑马鱼胚胎暴露于0、50、100或200 mg/L的HFPO-TA中。结果表明，在120 hpf时，HFPO-TA的50%致死浓度（LC）为231 mg/L，低于PFOA。HFPO-TA暴露降低了胚胎的孵化率、存活率和体长。此外，HFPO-TA在规格期比分化和成熟期表现出更高的毒性，导致Tg（fabp10a：DsRed）转基因幼虫肝脏体积变小和组织病理学变化。观察到与肝脏形成相关基因的mRNA表达显著下降。丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBIL）和直接胆红素（DBIL）水平显著升高。HFPO-TA降低了总胆固醇（TCHO）和甘油三酯（TG）活性，通过过氧化物酶体增殖物激活受体（PPAR）途径扰乱脂质代谢，并诱导炎症反应。此外，HFPO-TA抑制了Tg（Tp1：eGFP）转基因幼虫的肝内胆管发育，并干扰了与胆管发育相关基因的转录。HFPO-TA减少了胆汁酸合成但增加了胆汁酸转运，导致胆汁酸代谢紊乱。因此，HFPO-TA影响胚胎肝脏和胆道系统形态发生，导致肝脏损伤，可能是PFOA的不安全替代品。
