Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France.
Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France.
Environ Pollut. 2023 Aug 15;331(Pt 2):121882. doi: 10.1016/j.envpol.2023.121882. Epub 2023 May 24.
Human membrane drug transporters are recognized as major actors of pharmacokinetics; they also handle endogenous compounds, including hormones and metabolites. Chemical additives present in plastics interact with human drug transporters, which may have consequences for the toxicokinetics and toxicity of these widely-distributed environmental and/or dietary pollutants, to which humans are highly exposed. The present review summarizes key findings about this topic. In vitro assays have demonstrated that various plastic additives, including bisphenols, phthalates, brominated flame retardants, poly-alkyl phenols and per- and poly-fluoroalkyl substances, can inhibit the activities of solute carrier uptake transporters and/or ATP-binding cassette efflux pumps. Some are substrates for transporters or can regulate their expression. The relatively low human concentration of plastic additives from environmental or dietary exposure is a key parameter to consider to appreciate the in vivo relevance of plasticizer-transporter interactions and their consequences for human toxicokinetics and toxicity of plastic additives, although even low concentrations of pollutants (in the nM range) may have clinical effects. Existing data about interactions of plastic additives with drug transporters remain somewhat sparse and incomplete. A more systematic characterization of plasticizer-transporter relationships is needed. The potential effects of chemical additive mixtures towards transporter activities and the identification of transporter substrates among plasticizers, as well as their interactions with transporters of emerging relevance deserve particular attention. A better understanding of the human toxicokinetics of plastic additives may help to fully integrate the possible contribution of transporters to the absorption, distribution, metabolism and excretion of plastics-related chemicals, as well as to their deleterious effects towards human health.
人源膜药物转运体被认为是药代动力学的主要参与者；它们还处理包括激素和代谢物在内的内源性化合物。塑料中存在的化学添加剂会与人体药物转运体相互作用，这可能会对这些广泛分布的环境和/或饮食污染物的毒代动力学和毒性产生影响，而人类对此类污染物暴露程度极高。本综述总结了该主题的关键发现。体外实验表明，各种塑料添加剂，包括双酚类、邻苯二甲酸酯、溴化阻燃剂、多烷基酚和全氟及多氟烷基物质，可抑制溶质载体摄取转运体和/或 ATP 结合盒外排泵的活性。其中一些是转运体的底物，或可调节其表达。从环境或饮食暴露中获得的人体塑料添加剂浓度相对较低，是评估增塑剂-转运体相互作用及其对人体毒代动力学和塑料添加剂毒性的体内相关性的关键参数，尽管即使是低浓度的污染物（纳摩尔范围内）也可能具有临床意义。关于塑料添加剂与药物转运体相互作用的现有数据仍然有些稀疏和不完整。需要更系统地描述增塑剂-转运体关系。需要特别关注化学添加剂混合物对转运体活性的潜在影响，以及确定增塑剂中的转运体底物及其与新兴相关转运体的相互作用。更好地了解塑料添加剂的人体毒代动力学，可能有助于充分整合转运体对与塑料相关的化学物质的吸收、分布、代谢和排泄的可能贡献，以及它们对人类健康的有害影响。
