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Effects of flavonoid mixtures on the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers: An in vitro and kinetic modeling approach to predict the combined effects on transporter inhibition

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Author: Schutte, M.E. · Boersma, M.G. · Verhallen, D.A.M. · Groten, J.P. · Rietjens, I.M.C.M.
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:Food and Chemical Toxicology, 2, 46, 557-566
Identifier: 240633
doi: doi:10.1016/j.fct.2007.08.038
Keywords: ABC transporters · Caco-2 · Flavonoids · Kinetic modeling · Mixtures · PhIP · 2 amino 1 methyl 6 phenylimidazo[4,5 b]pyridine · Biological Transport, Active · Caco-2 Cells · Carcinogens · Drug Synergism · Flavonoids · Humans · Imidazoles · Models, Biological

Abstract

This study describes and kinetically models the effect of flavonoid mixtures on PhIP transport through Caco-2 monolayers. Previously it was shown that quercetin, luteolin, naringenin and myricetin increase the apical to basolateral PhIP transport in Caco-2 monolayers. In this study, apigenin was shown to exert a similar effect with an apparent Ki value of 10.8 μM. Additional experiments revealed that several binary flavonoid mixtures and one mixture containing all five model flavonoids increased the apical to basolateral PhIP transport through the Caco-2 monolayer. Assuming competitive inhibition of the apparent active transporter by the flavonoids and concentration-additivity for their inhibiting effect, the kinetic model previously developed to describe the effect of the individual flavonoids on PhIP transport, could be extended and adequately describes the experimental values obtained for the flavonoid mixtures. We conclude that combinations of flavonoids increase the transport of PhIP and do so by interacting in an additive way with the active transport of PhIP. This flavonoid-mediated increase in PhIP transport through Caco-2 monolayers may point at a possible increased bioavailability of PhIP in the presence of flavonoid mixtures in the in vivo situation. This would imply an adverse effect of these supposed beneficial food ingredients. © 2007 Elsevier Ltd. All rights reserved. Chemicals / CAS: 2 amino 1 methyl 6 phenylimidazo[4,5 b]pyridine, 105650-23-5; 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 105650-23-5; Carcinogens; Flavonoids; Imidazoles