Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances: Evidence from Experimental and Computational Studies
Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances: Evidence from Experimental and Computational Studies
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肠肝循环对全氟烷基和多氟烷基物质积累的影响：来自实验和计算研究的证据
DOI：
10.1021/acs.est.1c07176
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发表时间：
2022-03-01
影响因子：
11.4
通讯作者：
Liang, Yong
中科院分区：
文献类型：
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作者：
Cao, Huiming;Zhou, Zhen;Liang, Yong
全氟和多氟烷基物质（PFAS）的药代动力学特性影响其在生物系统中的分布和生物富集。肠肝循环导致某些化学物质从胆汁重吸收回血液和肝脏，从而影响其消除，但其对PFAS生物蓄积的影响仍不清楚。我们探讨了肠肝循环在PFAS生物蓄积的作用，通过检查各种PFAS在野生鱼类和大鼠模型中的组织分布。计算模型被用来确定PFAS的重吸收分数，通过计算结合亲和力的PFAS的关键转运蛋白的肠肝循环。结果表明，与鱼类的其他组织相比，在血液、肝脏和胆汁中观察到的某些全氟辛烷磺酸浓度较高。此外，在大鼠模型上暴露于PFAS混合物表明，大多数长链PFAS在8-12 h内出现重吸收现象。分子对接计算表明，PFAS可以通过静电和疏水相互作用与关键转运蛋白结合。进一步的回归分析增加了对以下假设的支持，即顶端钠依赖性胆汁酸转运蛋白的结合亲和力是预测PFAS人体半衰期的最重要变量。本研究证实了肠肝循环在PFAS的重吸收、分布和蓄积中的关键作用。
The pharmacokinetic characteristics of per- and polyfluoroalkyl substances (PFAS) affect their distribution and bioaccumulation in biological systems. The enterohepatic circulation leads to reabsorption of certain chemicals from bile back into blood and the liver and thus influences their elimination, yet its influence on PFAS bioaccumulation remains unclear. We explored the role of enterohepatic circulation in PFAS bioaccumulation by examining tissue distribution of various PFAS in wild fish and a rat model. Computational models were used to determine the reabsorbed fractions of PFAS by calculating binding affinities of PFAS for key transporter proteins of enterohepatic circulation. The results indicated that higher concentrations were observed in blood, the liver, and bile compared to other tissues for some PFAS in fish. Furthermore, exposure to a PFAS mixture on the rat model showed that the reabsorption phenomenon appeared during 8-12 h for most long-chain PFAS. Molecular docking calculations suggest that PFAS can bind to key transporter proteins via electrostatic and hydrophobic interactions. Further regression analysis adds support to the hypothesis that binding affinity of the apical sodium-dependent bile acid transporter is the most important variable to predict the human half-lives of PFAS. This study demonstrated the critical role of enterohepatic circulation in reabsorption, distribution, and accumulation of PFAS.