Quercetin increases the bioavailability of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats

Add time:09/04/2019    Source:sciencedirect.com

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.

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