Relevance of apical drug efflus pumps for intestinal flavonoid absorption

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Flavonoids occuring ubiquitously in food plants are discussed to be cardioprotective and to prevent cancer initiation and progression. Adverse effects, on the other hand, have also been described for selected flavonoids. In this respect risk-benefit analysis becomes the prime issue when it comes to dietary intake of non-nutrient food ingredients in particular when provided in supplements or functional foods. As part of the proposed safety assessment of secondary plant metabolites we shall focus on the cytoxic effects of selected flavonoids and on their bioavailability. Intestinal cells are by nature exposed to the highest levels of food derived compounds. Consequently, we will use human intestinal cells in culture as an in vitro model that allows potential cytotoxicity and its dose dependency to be assessed for a large number of flavonoids under identical experimental conditions. Investigations on the interactions of flavonoids with ATP-dependent efflux pumps for lipophilic compounds will indicate influence on their bioavailability as well as significant interactions with the transport of lipohilic xenobiotics including a large variety of drugs. The extent by which the efflux pumps affect the bioavailability of flavonoids will be investigated finally by comparing the transepithelial fluxes of selected radiolabeled flavonoids in the absence or presence of classical inhibitors for ATP-dependent efflux pumps.