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Pesticide biochemistry and physiology. 2025 Aug:212:106456. doi: 10.1016/j.pestbp.2025.106456 Q14.02025

Transepithelial transport and mechanism of pyrethroids across Caco-2 cells mediated by transporters

转运蛋白介导的除虫菊酯类化合物跨CaCo-2细胞上皮转运及机制研究 翻译改进

Yuying Liu  1, Sai Zhang  2, Tingting Li  2, Chang Chen  1, Shuyan Gui  1, Ziqi Liu  1, Jinjing Xiao  1, Haiqun Cao  1, Yanhong Shi  3

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作者单位

  • 1 Key Laboratory of Agri-products Quality and Biosafety (Anhui Agricultural University), Ministry of Education, Hefei, Anhui Province 230036, China; Joint Research Center for Food Nutrition and Health of IHM, School of Plant Protection, Anhui Agricultural University, Hefei, China.
  • 2 Key Laboratory of Agri-products Quality and Biosafety (Anhui Agricultural University), Ministry of Education, Hefei, Anhui Province 230036, China; School of Resource & Environment, Anhui Agricultural University, Hefei, Anhui Province 230036, China.
  • 3 Key Laboratory of Agri-products Quality and Biosafety (Anhui Agricultural University), Ministry of Education, Hefei, Anhui Province 230036, China; School of Resource & Environment, Anhui Agricultural University, Hefei, Anhui Province 230036, China. Electronic address: syh@ahau.edu.cn.
  • DOI: 10.1016/j.pestbp.2025.106456 PMID: 40500064

    摘要 中英对照阅读

    Oral ingestion is the primary route of human exposure to pesticide residues in agricultural products, with intestinal absorption playing a pivotal role in determining their bioavailability. This study investigated the transepithelial transport mechanisms of pyrethroids using a Caco-2 cell model. Apparent permeability coefficients (Papp) indicated that pyrethroids are readily absorbed, with efflux ratios (ER) ranging from 1.27 × 10-3 to 5.52 × 10-2, suggesting passive diffusion as the primary transport mode. Both efflux and influx transporters were involved in pyrethroids transport. Molecular docking showed that hydrophobic interactions contribute to the high binding affinity of lambda-cyhalothrin toward P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP). Metabolomics further identified P-gp, MRP, and BCRP as key ATP-binding cassette transporters mediating lambda-cyhalothrin transport, with hypoxanthine and pantothenic acid as significant differential metabolites. These findings underscore the role of transporters in pesticide residue absorption, providing valuable insights into human exposure assessment.

    Keywords: Caco-2 cell; Metabolomics; Molecular docking; Pyrethroids; Transporters.

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    口服摄入是人类接触农产品中农药残留的主要途径,肠道吸收在决定其生物利用度方面起着关键作用。本研究使用Caco-2细胞模型调查了拟除虫菊酯的跨上皮转运机制。表观渗透性系数(Papp)表明,拟除虫菊酯易于被吸收,外排比值(ER)在1.27 × 10-3到5.52 × 10-2之间变化,这表明被动扩散是主要的转运方式。外排和内向转运蛋白都参与了拟除虫菊酯的转运过程。分子对接显示,疏水相互作用有助于λ-氯氟氰菊酯与P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)和乳腺癌耐药蛋白(BCRP)的高度结合亲和力。代谢组学进一步确定了P-gp、MRP和BCRP作为介导λ-氯氟氰菊酯转运的关键ATP结合盒式转运蛋白,次黄嘌呤和泛酸是重要的差异代谢物。这些发现强调了转运蛋白在农药残留吸收中的作用,并为人类暴露评估提供了有价值的见解。

    关键词:Caco-2细胞;代谢组学;分子对接;拟除虫菊酯;转运蛋白。

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    期刊名:Pesticide biochemistry and physiology

    缩写:PESTIC BIOCHEM PHYS

    ISSN:0048-3575

    e-ISSN:1095-9939

    IF/分区:4.0/Q1

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    Transepithelial transport and mechanism of pyrethroids across Caco-2 cells mediated by transporters