Micro- and nanoplastics (MPs/NPs) constitute emerging and widely-distributed environmental contaminants to which humans are highly exposed. They possibly represent a threat for human health. In order to identify cellular/molecular targets for these plastic particles, we have analysed the effects of exposure to manufactured polystyrene (PS) MPs and NPs on in vitro activity and expression of human membrane drug transporters, known to interact with chemical pollutants. PS MPs and NPs, used at various concentrations (1, 10 or 100 µg/mL), failed to inhibit efflux activities of the ATP-binding cassette (ABC) transporters P-glycoprotein, MRPs and BCRP in ABC transporter-expressing cells. Furthermore, PS particles did not impair the transport of P-glycoprotein or BCRP substrates across intestinal Caco-2 cell monolayers. Uptake activities of solute carriers (SLCs) such as OCT1 and OCT2 (handling organic cations) or OATP1B1, OATP1B3, OATP2B1, OAT1 and OAT3 (handling organic anions) were additionally not altered by PS MPs/NPs in HEK-293 cells overexpressing these SLCs. mRNA expression of ABC transporters and of the SLCs OCT1 and OATP2B1 in Caco-2 cells and human hepatic HepaRG cells were finally not impaired by a 48-h exposure to MPs/NPs. Altogether, these data indicate that human drug transporters are unlikely to be direct and univocal targets for synthetic PS MPs/NPs.

中文翻译：

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聚苯乙烯微塑料和纳米塑料对人类药物转运蛋白活性和表达缺乏影响


微塑料和纳米塑料 （MP/NP） 是人类高度暴露的新兴且分布广泛的环境污染物。它们可能对人类健康构成威胁。为了确定这些塑料颗粒的细胞/分子靶标，我们分析了暴露于人造聚苯乙烯 （PS） MP 和 NP 对已知与化学污染物相互作用的人膜药物转运蛋白的体外活性和表达的影响。以不同浓度 （1、10 或 100 μg/mL） 使用的 PS MP 和 NPs 未能抑制 ABC 转运蛋白表达细胞中 ATP 结合盒 （ABC） 转运蛋白 P-糖蛋白、MRP 和 BCRP 的外排活性。此外，PS 颗粒不会损害 P-糖蛋白或 BCRP 底物跨肠道 Caco-2 细胞单层的转运。溶质载体 （SLC） 的摄取活性，如 OCT1 和 OCT2（处理有机阳离子）或 OATP1B1、OATP1B3、OATP2B1、OAT1 和 OAT3（处理有机阴离子）在过表达这些 SLC 的 HEK-293 细胞中也没有被 PS MP/NP 改变。Caco-2 细胞和人肝 HepaRG 细胞中 ABC 转运蛋白以及 SLCsOCT1 和 OATP2B1 的 mRNA 表达最终不会因暴露于 MPs/NPs 48 小时而受损。 这些数据表明，人类药物转运蛋白不太可能成为合成 PS MP/NP 的直接和单一靶标。