Interactions of organophosphate flame retardants with human drug transporters
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, wh...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323008527 |
| _version_ | 1827816167985643520 |
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| author | Valentin Tastet Marc Le Vée Marie Kerhoas Anna Zerdoug Elodie Jouan Arnaud Bruyère Olivier Fardel |
| author_facet | Valentin Tastet Marc Le Vée Marie Kerhoas Anna Zerdoug Elodie Jouan Arnaud Bruyère Olivier Fardel |
| author_sort | Valentin Tastet |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:10:58Z |
| format | Article |
| id | doaj.art-3f0cd1b2c257427e9b55b3e02e28499a |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-12T00:10:58Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-3f0cd1b2c257427e9b55b3e02e28499a2023-09-16T05:28:31ZengElsevierEcotoxicology and Environmental Safety0147-65132023-09-01263115348Interactions of organophosphate flame retardants with human drug transportersValentin Tastet0Marc Le Vée1Marie Kerhoas2Anna Zerdoug3Elodie Jouan4Arnaud Bruyère5Olivier Fardel6Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceUniv Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé), France; Correspondence to: Irset, Faculté de Pharmacie, 2 Avenue Pr Léon Bernard, 35043 Rennes, France.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.http://www.sciencedirect.com/science/article/pii/S0147651323008527Drug transporterFlame retardantsHepatic cellsHuman exposurePollutantToxicokinetics |
| spellingShingle | Valentin Tastet Marc Le Vée Marie Kerhoas Anna Zerdoug Elodie Jouan Arnaud Bruyère Olivier Fardel Interactions of organophosphate flame retardants with human drug transporters Ecotoxicology and Environmental Safety Drug transporter Flame retardants Hepatic cells Human exposure Pollutant Toxicokinetics |
| title | Interactions of organophosphate flame retardants with human drug transporters |
| title_full | Interactions of organophosphate flame retardants with human drug transporters |
| title_fullStr | Interactions of organophosphate flame retardants with human drug transporters |
| title_full_unstemmed | Interactions of organophosphate flame retardants with human drug transporters |
| title_short | Interactions of organophosphate flame retardants with human drug transporters |
| title_sort | interactions of organophosphate flame retardants with human drug transporters |
| topic | Drug transporter Flame retardants Hepatic cells Human exposure Pollutant Toxicokinetics |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323008527 |
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