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Neonicotinoid pesticides poorly interact with human drug transporters.

Journal of biochemical and molecular toxicology (2019-08-01)
Marc Le Vée, Astrid Bacle, Arnaud Bruyere, Olivier Fardel
ABSTRACT

The interactions of six neonicotinoid pesticides and one neonicotinoid metabolite with drug transporters have been characterized in vitro. Acetamiprid, clothianidin, imidacloprid, nitenpyram, thiacloprid and its metabolite thiacloprid amide, and thiamethoxam, each used at 100 µM, did not impair activity of the efflux pumps P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance protein. They also did not inhibit that of the uptake transporters OATP1B1, OATP1B3, OAT4, and MATE1, whereas that of OATP2B1, OAT1, and MATE2-K was affected by only one of the seven neonicotinoids. Activity of OCT1 was moderately stimulated (up to 1.5-fold) by several neonicotinoids. By contrast, that of OAT3 and OCT2 was inhibited by most (OAT3), if not all (OCT2), neonicotinoids, with IC50 values in the 20 to 60 µM range for thiacloprid, likely not relevant to environmental exposure. Thiacloprid was moreover not transported by OAT3 and OCT2. Overall, these data suggest that neonicotinoid pesticides rather poorly interact with drug transporter activities.

MATERIALS
Product Number
Brand
Product Description

Supelco
Nitenpyram, PESTANAL®, analytical standard
Sigma-Aldrich
Sulfobromophthalein disodium salt hydrate, used to study hepatocyte transport functions
Supelco
Clothianidin, PESTANAL®, analytical standard
Supelco
Thiamethoxam, PESTANAL®, analytical standard
Supelco
N-(6-Chloro-3-pyridylmethyl)-N-cyano-N-methylacetamidine, PESTANAL®, analytical standard
Sigma-Aldrich
6-Carboxyfluorescein, ~97% (HPLC)
Sigma-Aldrich
4′,5′-Dibromofluorescein, Dye content 95 %
Sigma-Aldrich
Fumitremorgin C, from Neosartorya fischeri, film
Supelco
Thiacloprid, PESTANAL®, analytical standard
Supelco
Thiacloprid-amide, PESTANAL®, analytical standard
Sigma-Aldrich
Pentostatin, ≥95% (HPLC)