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

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 (P_app) 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.