title: The transepithelial transport mechanism of polybrominated diphenyl ethers in human intestine determined using a Caco-2 cell monolayer.
abstract: Oral ingestion plays an important role in human exposure to polybrominated diphenyl ethers (PBDEs). The uptake of PBDEs primarily occurs in the small intestine. The aim of the present study is to investigate the transepithelial transport characteristics and mechanisms of PBDEs in the small intestine using a Caco-2 cell monolayer model. The apparent permeability coefficients of PBDEs indicated that tri- to hepta-BDEs were poorly absorbed compounds. A linear increase in transepithelial transport was observed with various concentrations of PBDEs, which suggested that passive diffusion dominated their transport at the concentration range tested. In addition, the pseudo-first-order kinetics equation can be applied to the transepithelial transport of PBDEs. The rate-determining step in transepithelial transport of PBDEs was trans-cell transport including the trans-pore process. The significantly lower transepithelial transport rates at low temperature for bidirectional transepithelial transport suggested that an energy-dependent transport mechanism was involved. The efflux transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) and influx transporters (organic cation transporters) participated in the transepithelial transport of PBDEs. In addition, the transepithelial transport of PBDEs was pH sensitive; however, more information is required to understand the influence of pH.
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China. Electronic address: yuyingxin@staff.shu.edu.cn.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Kaiqiong
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Bingli
authors.initials: B
authors.lastname: Lei
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells / Q000187:drug effects; D002470:Cell Survival; D002927:Cimetidine / Q000494:pharmacology; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D055768:Halogenated Diphenyl Ethers / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D009363:Neoplasm Proteins; D002927:Cimetidine
keywords: Caco-2 cell monolayer; Efflux transporter; Influx transporter; Polybrominated biphenyl ethers; Transepithelial transport