Relevance of apical drug efflus pumps for intestinal flavonoid absorption

在食用植物中普遍存在的类黄酮类化合物被认为具有心脏保护作用，并可防止癌症的发生和发展。另一方面，一些黄酮类化合物的副作用也已被描述。在这方面，当涉及非营养性食品成分的膳食摄入时，尤其是在补充剂或功能性食品中提供非营养性食品成分时，风险-效益分析成为首要问题。作为拟议的次生植物代谢物安全性评估的一部分，我们将重点放在选定的黄酮类化合物的细胞毒性效应及其生物利用度上。肠道细胞天生接触最高水平的食物衍生化合物。因此，我们将使用培养的人肠道细胞作为体外模型，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。研究类黄酮类化合物与依赖于ATP的脂类化合物外排泵之间的相互作用将会对其生物利用度产生影响，并与包括多种药物在内的亲脂性外源化合物的运输产生显著的相互作用。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在没有或存在经典的ATP依赖的外排泵抑制剂的情况下，选定的放射性标记黄酮类化合物的跨皮流量来进行研究。

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.