Relevance of apical drug efflus pumps for intestinal flavonoid absorption

在食用植物中普遍存在的黄酮类化合物被认为具有保护心脏和防止癌症发生和发展的作用。另一方面，对某些黄酮类化合物的副作用也有描述。在这方面，风险效益分析成为主要问题，当涉及到膳食摄入非营养食品成分，特别是当补充剂或功能食品提供。作为次生植物代谢物安全性评估的一部分，我们将重点关注选定的类黄酮的细胞毒性作用及其生物利用度。肠道细胞天生就暴露在最高水平的食物衍生化合物中。因此，我们将使用培养的人类肠细胞作为体外模型，允许在相同的实验条件下评估大量黄酮类化合物的潜在细胞毒性及其剂量依赖性。研究类黄酮与atp依赖的亲脂化合物外排泵的相互作用将表明其对生物利用度的影响，以及与包括多种药物在内的亲脂异种生物转运的重要相互作用。外排泵对黄酮类化合物生物利用度的影响程度将通过比较选定的放射性标记黄酮类化合物在没有或存在atp依赖性外排泵的经典抑制剂的情况下的经上皮通量来研究。

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.