Title
Quercetin increases the bioavailability of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats
Author
Schutte, M.E.
Alink, G.M.
Freidig, A.P.
Spenkelink, B.
Vaessen, J.C.H.
van de Sandt, J.J.M.
Groten, J.P.
Rietjens, I.M.C.M.
TNO Kwaliteit van Leven
KvL
Publication year
2008
Abstract
This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h) for rats dosed with PhIP alone. Significantly increased blood PhIP levels were detected at 15, 30, 45 and 180 min. At 4 and 8 h post-dosing a difference in the PhIP levels in the blood between the two treatment groups was no longer observed. In vitro and in silico modeling of PhIP transport using Caco-2 cells and a previously described kinetic model for PhIP transport revealed that the relative increase in PhIP transport caused by quercetin is dependent on the concentration of the two compounds. When substituting the PhIP and quercetin concentrations used in the in vivo experiment in the kinetic model, an effect of quercetin on PhIP transport was predicted that matches the actual effect of 131% observed in vivo. It is concluded that quercetin increases the bioavailability of the pro-carcinogen PhIP in rats pointing at a potential adverse effect of this supposed beneficial food ingredient. © 2008 Elsevier Ltd. All rights reserved. Chemicals / CAS: 2 amino 1 methyl 6 phenylimidazo[4,5 b]pyridine, 105650-23-5; quercetin, 117-39-5; 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, 105650-23-5; Antioxidants; Carcinogens; Imidazoles; Quercetin, 117-39-5
Subject
Biology
Biomedical Research
ABC transporters
Caco-2 monolayers
In silico modelling
PhIP
Quercetin
Rat
2 amino 1 methyl 6 phenylimidazo[4,5 b]pyridine
quercetin
animal experiment
animal tissue
article
bioavailability
cell strain CACO 2
computer model
controlled study
dietary intake
human
human cell
in vitro study
in vivo study
male
nonhuman
rat
Animals
Antioxidants
Area Under Curve
Biological Availability
Biological Transport, Active
Caco-2 Cells
Carcinogens
Humans
Imidazoles
Male
Models, Biological
Quercetin
Random Allocation
Rats
Rats, Wistar
Rattus
To reference this document use:
http://resolver.tudelft.nl/uuid:cb55f0f3-31bf-4e4f-af43-64f4066e59a9
DOI
https://doi.org/10.1016/j.fct.2008.08.015
TNO identifier
241103
ISSN
0278-6915
Source
Food and Chemical Toxicology, 46 (11), 3422-3428
Document type
article