Bruyere Arnaud, Hubert Céline, Le Vee Marc, Chedik Lisa, Sayyed Katia, Stieger Bruno, Denizot Claire, Parmentier Yannick, Fardel Olivier
Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France.
Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France; EDST-AZM-center-LBA3B, Faculty of Sciences, Rafic Hariri Campus, Lebanese University, Lebanon.
Toxicol In Vitro. 2017 Apr;40:34-44. doi: 10.1016/j.tiv.2016.12.009. Epub 2016 Dec 15.
The plastic component bisphenol A (BPA) is suspected to exert deleterious effects towards human health and targets various cellular and molecular pathways, including activity of ATP-binding cassette drug transporters. The present study was designed to determine whether BPA and some derivatives, like its substitutes bisphenol F (BPF) and bisphenol S (BPS) and the flame retardant tetrabromobisphenol A (TBBPA), may additionally interact with solute carrier (SLC) drug transporters. Activities of the various following SLC transporters were inhibited in a major way (by >60%) by 100μM bisphenols: OCT1 and MATE1 (by BPA and TBBPA), OATP1B1 (by BPA, BPF and TBBPA), OATP1B3 and NTCP (by TBBPA) and OAT3 (by BPA, BPF, BPS and TBBPA); by contrast, activities of other transporters were not impacted (MATE2-K) or were stimulated (notably OCT1 by BPS and OCT2 by BPF). Transporter inhibitions due to bisphenols were concentrations-dependent, with half maximal inhibitory concentrations (IC) ranging from 0.5μM to 73.5μM. BPA was finally shown to be not transported by OAT3, although inhibiting this transporter in a competitive manner. Taken together, these data indicate that bisphenols interact with SLC transporters, at concentration levels however rather higher than those occurring in humans in response to environmental exposure.
塑料成分双酚A（BPA）被怀疑会对人体健康产生有害影响，并作用于各种细胞和分子途径，包括ATP结合盒式药物转运体的活性。本研究旨在确定BPA及其一些衍生物，如替代物双酚F（BPF）和双酚S（BPS）以及阻燃剂四溴双酚A（TBBPA），是否还会与溶质载体（SLC）药物转运体相互作用。100μM双酚对以下各种SLC转运体的活性有显著抑制作用（>60%）：OCT1和MATE1（受BPA和TBBPA抑制）、OATP1B1（受BPA、BPF和TBBPA抑制）、OATP1B3和NTCP（受TBBPA抑制）以及OAT3（受BPA、BPF、BPS和TBBPA抑制）；相比之下，其他转运体的活性未受影响（MATE2-K）或受到刺激（特别是BPS刺激OCT1，BPF刺激OCT2）。双酚对转运体的抑制作用呈浓度依赖性，半数最大抑制浓度（IC）范围为0.5μM至73.5μM。尽管BPA以竞争性方式抑制OAT3，但最终表明它不会被OAT3转运。综上所述，这些数据表明双酚与SLC转运体相互作用，然而其浓度水平高于人体因环境暴露而产生的浓度。
