Binding of per- and polyfluoroalkyl substances with liver and serum proteins in rats: implications for physiologically based pharmacokinetic modelling

文献类型： 外文期刊

第一作者： Fan, Xiarui

作者： Fan, Xiarui;Li, Xiaomin;Fan, Wenhong;Wang, Xiangrui;Wang, Ziwei;Dong, Zhaomin;Li, Tong;Shao, Bing;Niu, Shan;Wang, Qi;Zhong, Lv;Zheng, Guomao;Ma, Fujun;Peng, Hui;Peng, Hui;Peng, Hui;Chen, Lili;Dong, Zhaomin

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关键词： PFAS; Protein binding; PBPK model; Liver-blood partition; Toxicokinetics

期刊名称：ENVIRONMENT INTERNATIONAL （ 影响因子：9.7； 五年影响因子：11.6 ）

ISSN： 0160-4120

年卷期： 2025 年 201 卷

页码：

收录情况： SCI

摘要： Understanding the binding between per- and polyfluoroalkyl substances (PFAS) and proteins is essential for elucidating their toxicokinetics and tissue distribution. Here, we quantified the binding affinities of 14 PFAS to rat liver fatty acid-binding protein (rL-FABP) and rat serum albumin (RSA). Results showed that PFAS exhibit strong binding affinities (K-a) to the rL-FABP (10(3) similar to 10(5) M-1), particularly among medium- to long-chain perfluorinated carboxylic acids (PFCAs). The binding affinity of PFAS to RSA ranged from approximately 10(4) to 10(5) M-1, with 1 to 4 binding sites. Molecular docking results supported that PFAS binding to proteins is an exothermic process driven by van der Waals forces, hydrogen bonding, and electrostatic interactions. Additionally, long-chain PFCAs were shown to adopt a "U"-shaped conformation within the ligand-binding cavities of rL-FABP and RSA. The newly developed physiologically based pharmacokinetic model using measured binding data demonstrates a substantial improvement in the goodness of fit to experimental observations, reducing the prediction error by 20 %similar to 216 %. Finally, we found that the PFAS liver-blood partition could be mainly explained by the binding affinity ratios of PFAS to liver and blood proteins, which could be further extrapolated from rats to humans, providing useful insights to understand the tissue distribution of PFAS.

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