Inhibition of SLC drug transporter activities by environmental bisphenols

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...

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Published in:Toxicology in vitro Vol. 40; pp. 34 - 44
Main Authors: Bruyere, Arnaud, Hubert, Céline, Le Vee, Marc, Chedik, Lisa, Sayyed, Katia, Stieger, Bruno, Denizot, Claire, Parmentier, Yannick, Fardel, Olivier
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.04.2017
Elsevier Science Ltd
Elsevier
Subjects:
ABC transporters
Adenosine triphosphate
Benzhydryl Compounds - pharmacology
Bisphenol A
Bisphenol F
Bisphenol S
Bisphenols
Cell Line, Tumor
Drug transporters
Ecology, environment
Estrogens
Flame retardants
HEK293 Cells
Humans
Inhibition
Life Sciences
Oct-2 protein
Organic Anion Transporters, Sodium-Independent - antagonists & inhibitors
Organic Anion Transporters, Sodium-Independent - genetics
Organic Anion Transporters, Sodium-Independent - metabolism
Organic Cation Transport Proteins - antagonists & inhibitors
Organic Cation Transport Proteins - genetics
Organic Cation Transport Proteins - metabolism
Phenols
Phenols - pharmacology
Polybrominated Biphenyls - pharmacology
Polycarbonate resins
Sulfones - pharmacology
Tetrabromobisphenol A
Bisphenol A
Bisphenol F
Inhibition
Tetrabromobisphenol A
Bisphenol S
Drug transporters
ISSN:0887-2333, 1879-3177, 1879-3177
Online Access:Get full text
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Summary: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 (IC50) 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. •Environmental bisphenols inhibited activities of various SLC drug transporters.•OCT1, MATE1 and OATP1B1 were thus notably targeted by bisphenol A.•Bisphenol A also competitively inhibited OAT3, without however being transported.•High concentrations of bisphenols were however needed for SLC transporter inhibitions.
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ISSN:0887-2333
1879-3177
1879-3177
DOI:10.1016/j.tiv.2016.12.009