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Article Dans Une Revue Xenobiotica Année : 2022

Interactions of organophosphorus pesticides with ATP-Binding Cassette (ABC) drug transporters

Résumé

Although pharmaceutical companies have to study drug-transporter interaction, environmental contaminant interactions with these transporters are not well characterised. In this study, we demonstrated using transfected cell line that some organophosphorus pesticides are able to interact with drug efflux transporters like P-glycoprotein, BCRP and MRPs.According to our results, dibrom was found to inhibit only Hoechst binding site of P-gp with an IC closed to 77 µM, phosmet inhibited BCRP efflux with an IC of 42 µM and only profenofos was able to inhibit BCRP, MRPs and P-gp at two binding sites. As profenofos appeared to be a potent ABC transporter inhibitor, we studied its potential substrate property towards P-gp.Using a docking approach, we developed an in silico tool to study pesticide properties to be a probe or inhibitor of P-gp transporter. From both and results, profenofos was not considered as a P-gp substrate.Combining both in vitro and docking methods appears to be an attractive approach to select pesticides that would not pass into the blood systemic circulation.

Domaines

Toxicologie
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Dates et versions

hal-03790186 , version 1 (28-09-2022)

Identifiants

Citer

Lisa Chedik, Dominique Mias-Lucquin, Olivier Fardel, Olivier Delalande, Arnaud Bruyère. Interactions of organophosphorus pesticides with ATP-Binding Cassette (ABC) drug transporters. Xenobiotica, 2022, 52 (6), pp.644-652. ⟨10.1080/00498254.2022.2128467⟩. ⟨hal-03790186⟩
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