Aberrant hepatic lipid metabolism associated with gut microbiota dysbiosis triggers hepatotoxicity of novel PFOS alternatives in adult zebrafish
Aberrant hepatic lipid metabolism associated with gut microbiota dysbiosis triggers hepatotoxicity of novel PFOS alternatives in adult zebrafish
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与肠道微生物群失调相关的肝脏脂质代谢异常会引发成年斑马鱼新型全氟辛烷磺酸替代品的肝毒性
DOI：
10.1016/j.envint.2022.107351
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发表时间：
2022
影响因子：
11.8
通讯作者：
Wenqing Tu
中科院分区：
文献类型：
--
作者：
Qiyu Wang;Jing Huang;Shuai Liu;Caiyun Wang;Yuanxiang Jin;Hong Lai;Wenqing Tu
据报告，全氟辛烷磺酸会导致野生动物和人类的肝中毒。在对全氟辛烷磺酸实施限制后，新型全氟辛烷磺酸替代品得到了广泛使用，但对其潜在毒性知之甚少。本研究首次通过组织病理学、生化检测和多组学分析对PFOS、6：2Cl-PFESA（F-53 B）和对全氟壬烯氧基苯磺酸钠（OBS）对成年斑马鱼的慢性肝毒性及其分子机制进行了全面研究。全氟辛烷磺酸及其替代品对肝脏组织病理学和肝功能指标的影响顺序为F-53 B> PFOS > OBS，这与其在肝脏中的浓度一致。计算机模拟和转录谱分析表明，F-53 B和PFOS诱导的肝脏脂质代谢异常是通过作用于过氧化物酶体增殖物激活受体γ（PPARγ），引发下游基因转录的变化，导致脂质合成与消耗失衡。肠道微生物组分析提供了另一种新的机制观点，即军团菌属、罗尔斯通氏菌属、短单胞菌属、α变形菌属、邻单胞菌属和丝微菌属丰度的变化可能与基于其显著相关性的PPAR途径的改变有关。本研究深入探讨了全氟辛烷磺酸及其新型替代品引起肝毒性的分子机制，并强调需要关注其环境接触风险。
Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions on PFOS, but little is known about their potential toxicity. Here, the first comprehensive investigation on the chronic hepatotoxicity and underlying molecular mechanisms of PFOS, 6:2Cl-PFESA (F-53B), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) was carried out on adult zebrafish through a histopathological examination, biochemical measurement, and multi-omics analysis. PFOS and its alternatives caused changes in liver histopathology and liver function indices in the order of F-53B > PFOS > OBS, which was consistent with their concentration in the liver. In silico modeling and transcriptional profiles suggested that the aberrant hepatic lipid metabolism induced by F-53B and PFOS was initiated by the action on peroxisome proliferator-activated receptor γ (PPARγ), which triggered changes in downstream genes transcription and led to an imbalance between lipid synthesis and expenditure. Gut microbiome analysis provided another novel mechanistic perspective that changes in the abundance of Legionella, Ralstonia, Brevundimonas, Alphaproteobacteria, Plesiomonas, and Hyphomicrobium might link to alterations in the PPAR pathway based on their significant correlation. This study provides insight into the molecular mechanisms of hepatotoxicity induced by PFOS and its novel alternatives and highlights the need for concern about their environmental exposure risks.