title: Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model.
abstract: In order to assess the risk to mammals of a chronic exposure to imidacloprid (IMI), we investigated its absorption with the human intestinal Caco-2 cell line. Measurements of transepithelial transport revealed an apparent permeability coefficient of 21.6 x 10(-6) +/- 3.2 x 10(-6) cm/s reflecting a 100% absorption. The comparison of apical to basal (A-B) and basal to apical (B-A) transports showed that the monolayer presents a basal to apical polarized transport. Studies of apical uptake demonstrated that the transport was concentration-dependent and not saturable from 5 to 200 microM. Arrhenius plot analysis revealed two apparent activation energies, Ea(4-12 degrees C) = 63.8 kJ/mol and Ea(12-37 degrees C) = 18.2 kJ/mol, suggesting two temperature-dependent processes. IMI uptake was equivalent when it was performed at pH 6.0 or 7.4. Depletion of Na+ from the transport buffer did not affect the uptake, indicating that a sodium-dependent transporter was not involved. Decrease of uptake with sodium-azide or after cell surface trypsin (Ti) treatment suggested the involvement of a trypsin-sensitive ATP-dependent transporter. Investigations on apical efflux demonstrated that initial velocities paralleled the increase of loading concentrations. A cell surface trypsin treatment did not affect the apical efflux. The lack of effect when the efflux was performed against an IMI concentration gradient suggested that an energy-dependent transporter was involved. However, the inhibition of P-glycoproteins (P-gp) and multidrug resistance-associated proteins (MRP) by taxol, vincristine, and daunorubicine had no effect on IMI intracellular accumulation suggesting the involvement of transporters distinct from classical ATP binding cassette transport (ABC-transport) systems. All results suggest that IMI is strongly absorbed in vivo by inward and outward active transporters.
authors.affiliation: Laboratoire de Toxicologie Environnementale, UMR 406 INRA-UAPV, INRA, Site Agroparc, 84914 Cedex 9, Avignon, France
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Brunet
authors.forename: Marc
authors.initials: M
authors.lastname: Maresca
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.forename: Luc P
authors.initials: LP
authors.lastname: Belzunces
mesh_terms: D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000502:physiology*; D000073943:Neonicotinoids; D009574:Nitro Compounds
chemical_list: D007093:Imidazoles; D000073943:Neonicotinoids; D009574:Nitro Compounds; C082359:imidacloprid