Effect of quercetin on the toxicokinetics of ochratoxin A in rats

Previous studies indicate that the intestinal absorption of the nephrotoxic mycotoxin ochratoxin A (OTA) occurs mainly through passive diffusion of the undissociated form. However, several in vitro studies have shown that OTA is partly re-secreted into the intestinal lumen by the multi-drug resistance associated protein (MRP2) and breast cancer resistance protein (BRCP). In vitro studies using Caco-2 cells have shown that some polyphenols (quercetin, genistein, resveratrol) may impair OTA efflux through competitive inhibition of MRP2, possibly resulting in an increased systemic availability of OTA. Among the tested polyphenols, quercetin showed the highest potential as efflux pump inhibitor; therefore, the aim of the present in vivo study was to investigate possible effects of quercetin on the toxicokinetics of OTA in rats. Eighteen growing male F344 Fisher rats (body weight: 200g) were allocated to two dietary treatments consisting of (1) a commercial, flavonoid-free balanced diet containing 10mg OTA/kg derived from inoculated wheat and (2) the same diet supplemented with 100mg quercetin/kg. The animals were fed restrictively (similar to 0.7 of ad libitum intake, 13g/d) to avoid differences in OTA intake. Animals were kept in metabolism cages to facilitate total urine and faeces collection. After 6 days on trial, rats were euthanised and blood, liver, kidney, muscle and brain samples were taken from each animal. Faeces, urine and tissue samples were analysed for OTA and its main metabolite ochratoxin by high-performance liquid chromatography using fluorescence detection. Quercetin supplementation had no effect (P>0.05) on feed consumption, OTA-intake, water intake and body weight gain. Faecal and urinary excretion of OTA and ochratoxin and concentrations of OTA in all tissues were not affected by quercetin supplementation. Based on the total excretion and tissue concentrations of OTA, it is concluded that the polyphenol quercetin has no impact on the toxicokinetics of OTA in vivo.