有机磷酸盐阻燃剂（OPFRs）是一种引起越来越多关注的环境污染物，在环境中广泛分布，并对人体健康可能产生不利影响。本研究对其与人体药物转运体的可能相互作用进行了体外研究，这些转运体是环境化学物质的靶点，也是其毒动力学的影响因素。一些OPFRs，如三（2-丁氧基乙基）磷酸酯（TBOEP）、三（1,3-二氯异丙基）磷酸酯（TDCPP）、三对甲酚酸酯（TOCP）和三苯基磷酸酯（TPHP），被发现抑制了一些转运体的活性，如有机阴离子转运体3（OAT3）、有机阴离子转运多肽（OATP）1B1、OATP1B3、有机阳离子转运体2（OCT2）或乳腺癌耐药蛋白（BCRP）。这些效应与浓度相关，IC50值范围从6.1µM（对于TDCPP介导的OCT2抑制）到51.4µM（对于TOCP介导的BCRP抑制）。OPFRs还阻断了转运体依赖的内源底物的细胞膜通过，尤其是激素的通过。然而，OAT3无法转运TBOEP和TPHP。OPFRs还抑制了培养人肝HepaRG细胞中一些转运体的mRNA表达，尤其是对TOCP反应中OAT2和OCT1的表达，其IC50值分别为2.3µM和2.5µM。因此，这些数据将OPFRs纳入与药物转运体相互作用的污染物不断扩大的列表中，尽管这些浓度范围在2-50µM，比人类环境或饮食暴露于这些化学物质时观察到的浓度较高。 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Organophosphate flame retardants (OPFRs) are environmental pollutants of increasing interest, widely distributed in the environment and exerting possible deleterious effects towards the human health. The present study investigates in vitro their possible interactions with human drug transporters, which are targets for environmental chemicals and actors of their toxicokinetics. Some OPFRs, i.e., tris(2-butoxyethyl) phosphate (TBOEP), tris(1,3-dichloroisopropyl) phosphate (TDCPP), tri-o-cresyl phosphate (TOCP) and triphenyl phosphate (TPHP), were found to inhibit activities of some transporters, such as organic anion transporter 3 (OAT3), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2 (OCT2) or breast cancer resistance protein (BCRP). These effects were concentration-dependent, with IC50 values ranging from 6.1 µM (for TDCPP-mediated inhibition of OCT2) to 51.4 µM (for TOCP-mediated inhibition of BCRP). OPFRs also blocked the transporter-dependent membrane passage of endogenous substrates, notably that of hormones. OAT3 however failed to transport TBOEP and TPHP. OPFRs additionally repressed mRNA expressions of some transporters in cultured human hepatic HepaRG cells, especially those of OAT2 and OCT1 in response to TOCP, with IC50 values of 2.3 µM and 2.5 µM, respectively. These data therefore add OPFRs to the expanding list of pollutants interacting with drug transporters, even if OPFR concentrations required to impact transporters, in the 2-50 µM range, are rather higher than those observed in humans environmentally or dietarily exposed to these chemicals.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.