Differential modulation of ochratoxin A absorption across Caco-2 cells by dietary polyphenols, used at realistic intestinal concentrations.
The effect of polyphenols (PPs) on the absorption of ochratoxin A (OTA), a food-borne mycotoxin, was investigated in an in vitro model of the human intestinal barrier based on Caco-2 cells cultivated in a bicameral system. Two intraluminal concentrations of OTA approaching physiological levels were chosen (0.75 nM and 7.5 nM) through calculations based on estimated daily intakes. The transport of OTA from the apical to the basolateral side of Caco-2 cells, i.e. absorption, was directly proportional to its initial apical concentration. Very significant increase in both OTA absorption and cellular accumulation was observed upon co-incubation with certain PPs, i.e. chrysin, quercetin, genistein, biochanin A, resveratrol, at concentrations that should be encountered in the gastrointestinal tract, as well as with MK571, a specific inhibitor of MRPs efflux pumps. As these PPs have been reported to be metabolized in Caco-2 cells into substrates of MRP-2, we hypothesize that PPs and/or metabolites could impair the OTA efflux, previously proposed to be mediated by the MRP-2, through competitive inhibition for the pump. These data imply that interactions between OTA and PPs may lead to a greater bioavailability of the mycotoxin in the bloodstream with possible adverse effects for human health.
Sergent
Thérèse
T
Laboratoire de Biochimie cellulaire, Institut des Sciences de la Vie & Université catholique de Louvain, Place Croix du Sud, B 1348 Louvain-la-Neuve, Belgium.
Garsou
Serge
S
Schaut
Annelore
A
De Saeger
Sarah
S
Pussemier
Luc
L
Van Peteghem
Carlos
C
Larondelle
Yvan
Y
Schneider
Yves-Jacques
YJ
D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002273:Carcinogens / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005502:Food; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors; D009793:Ochratoxins / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D013050:Spectrometry, Fluorescence
D002273:Carcinogens; D005419:Flavonoids; D007770:L-Lactate Dehydrogenase; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009793:Ochratoxins; D010636:Phenols; D059808:Polyphenols; C000715087:ABCC2 protein, human; C025589:ochratoxin A