Relevance of apical drug efflus pumps for intestinal flavonoid absorption

顶端药物流出泵与肠道类黄酮吸收的相关性

• 批准号: 5400626
• 负责人: Professor Dr. Uwe Wenzel
• 金额: --
• 依托单位: Professur für Biochemie und Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5400626?language=en
• 关键词: Relevance; apical; drug; efflus; pumps

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.

广泛存在于食用植物中的黄酮类化合物被认为具有心脏保护作用，可以预防癌症的发生和发展。另一方面，也描述了所选黄酮类化合物的副作用。在这方面，当涉及非营养食品成分的饮食摄入时，特别是当以补充剂或功能性食品的形式提供时，风险效益分析成为首要问题。作为植物次生代谢产物安全性评估的一部分，我们将重点关注所选黄酮类化合物的细胞毒性作用及其生物利用度。肠细胞自然暴露于最高水平的食物衍生化合物。因此，我们将使用培养的人肠细胞作为体外模型，其允许在相同的实验条件下对大量黄酮类化合物进行潜在的细胞毒性及其剂量依赖性评估。类黄酮与亲脂性化合物的ATP依赖性外排泵的相互作用的调查将表明其生物利用度的影响，以及显着的相互作用与亲脂性外源性物质，包括大量的各种药物的运输。外排泵影响黄酮类化合物生物利用度的程度将最终通过比较选择的放射性标记的黄酮类化合物在经典的ATP依赖性外排泵抑制剂的存在或不存在下的跨上皮通量进行研究。