title: Effect of quercetin on the uptake and efflux of aristolochic acid I from Caco-2 cell monolayers.
abstract: OBJECTIVE
  The purpose of this study was to determine whether quercetin decreases the uptake of aristolochic acid I (AAI) from the apical membranes of Caco-2 cells via H(+) -linked MCTs at neutral pH as well as to confirm the secretion of AAI through the Caco-2 cell monolayers via ABC transporters.
  
  
  METHODS
  Caco-2 cells cultured on the dishes or permeable membranes were incubated with AAI in the absence or presence of quercetin or transporter inhibitors.
  
  
  RESULTS
  Coincubation with quercetin decreased the uptake of AAI by Caco-2 cells cultured on the dishes at pH 7.4, and a similar decrease in AAI uptake was found when the cells were coincubated with acetic acid or benzoic acid. In contrast, the basolateral-to-apical transport of AAI was higher than the apical-to-basolateral transport of AAI at pH 7.4, and the former transport was decreased by quercetin and the BCRP inhibitors of Ko-143 and mitoxantrone, but not by P-gp or MRP2 inhibitors.
  
  
  CONCLUSIONS
  AAI appears to be secreted from the apical membranes of Caco-2 cells via BCRP at neutral pH, although a small amount of AAI is taken up from the apical membranes via H(+) -linked MCTs, and quercetin may decrease both the BCRP-mediated efflux and the MCT-mediated influx of AAI.
authors.affiliation: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.affiliation: Daiichi College of Pharmaceutical Sciences, Minami-Ku, Fukouka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Daiichi College of Pharmaceutical Sciences, Minami-Ku, Fukouka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.affiliation: Faculty of Nutritional Sciences, Nakamura Gakuen University, Johnan-Ku, Fukouka, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohta
authors.affiliation: Faculty of Nutritional Sciences, Nakamura Gakuen University, Johnan-Ku, Fukouka, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koga
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.affiliation: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D019342:Acetic Acid / Q000494:pharmacology; D034341:Aristolochic Acids / Q000493:pharmacokinetics*; D019817:Benzoic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects*; D018938:Caco-2 Cells; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D054659:Diketopiperazines / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D008942:Mitoxantrone / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
chemical_list: C541506:3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester; D018528:ATP-Binding Cassette Transporters; D034341:Aristolochic Acids; D054659:Diketopiperazines; D006576:Heterocyclic Compounds, 4 or More Rings; D011422:Propionates; D011804:Quinolines; C059141:verlukast; D016572:Cyclosporine; D019817:Benzoic Acid; C000228:aristolochic acid I; D011794:Quercetin; D008942:Mitoxantrone; D011802:Quinidine; D017035:Pravastatin; D019342:Acetic Acid; D007213:Indomethacin
keywords: Aristolochic acid I; Caco-2 cell; breast cancer resistance protein; monocarboxylic acid transporters; quercetin