The effects of selected flavonoids on cytochromes P450 in rat liver and small intestine

In recent years, the consumption and use of dietary supplements containing concentrated phytochemicals (e.g. flavonoids) increased dramatically. Flavonoids, as foreign compounds (xenobiotics), have great potential to modulate the activity of cytochrome P450s (CYPs), xenobiotic-metabolizing enzymes involved in the activation and detoxification of food and environmental carcinogens. Thus, the aim of this study was to investigate the effects of model glycosylated and deglycosylated flavonoids on CYPs in rat liver and small intestine, as the two main organs responsible for xenobiotic metabolism, after p.o. administration by gastric gavages. The effects of two glycosylated flavonoids (isoquercitrin, rutin) and their aglycone (quercetin) on CYPs were determined using Western blotting technique and specific activity assays with alkyl-resorufin derivatives. In liver microsomes, a considerable increase of all the measured marker activities (EROD, MROD, PROD) was observed only after isoquercitrin treatment. To evaluate the effects of flavonoids on CYPs along small intestine, the tissue was dissected into proximal (near pylorus), middle and distal parts. Of all the tested compounds, isoquercitrin was the most efficient CYP inducer, namely in the middle part of small intestine. Obtained data demonstrate the different effects of flavonoid glycosides and aglycone on CYP expression in rat liver and small intestine. Since these phytochemicals are xenobiotics, and thus they can increase the human risk of cancer development, their consumption in large quantities should be carefully considered.