Myricetin stimulates the absorption of the pro-carcinogen PhIP.
The effect of the flavonoid myricetin on the transport of the pro-carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through differentiated Caco-2 monolayers, a model for the intestinal epithelium, is described. Myricetin causes an increase of the transport of PhIP from the apical to the basolateral compartment. This effect was observed at physiologically relevant concentrations of PhIP and myricetin. Cyclosporin A (MRP2 inhibitor) but not PSC833 (P-gp inhibitor) showed a similar effect on PhIP transport. The results indicate that myricetin induces an increased basolateral uptake of the pro-carcinogen PhIP, in part through inhibition of the MRP2 mediated excretion of PhIP from the intestinal cells back to the lumen.
Schutte
Maaike E
ME
Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, The Netherlands. Maaike.schutte@wur.nl
van de Sandt
Johannes J M
JJ
Alink
Gerrit M
GM
Groten
John P
JP
Rietjens
Ivonne M C M
IM
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000042:Absorption; D018938:Caco-2 Cells; D002273:Carcinogens / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D026901:Membrane Transport Proteins / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010539:Permeability
D018528:ATP-Binding Cassette Transporters; D002273:Carcinogens; D005419:Flavonoids; D007093:Imidazoles; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C040015:myricetin; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine