Thermal Reaction Products of Ochratoxin A: Metabolism and Bioavailability

在热食品加工过程中，例如在咖啡烘焙或谷物挤压蒸煮过程中，各种化学反应都会导致真菌毒素赭曲霉毒素A(OTA)的降解。在第一个资助期，我们首次发现除了OTA异构化为14R-赭曲霉毒素A(14R-OTA)外，还发生了OTA与多糖的共价基质结合。此外，我们可以证明这些与基质结合的形式在咖啡冲泡过程中或在导致OTA释放的肠道代谢过程中被切割。除了第一个资助期外，我们还分析了咖啡和非咖啡饮用者的血液样本，以了解OTA和14R-OTA的发生情况。我们可以证明，在血液样本中可以检测到相对较高的14R-OTA，在某些情况下，与OTA相比，14R-OTA的水平更高。在下面的提案中，将研究这些高水平的原因。为此，计划进行机械学评估的体外研究以及人体体内研究。在体外实验中，将通过比较OTA和14R-OTA对猪盲肠模型的血浆蛋白结合力、肝、肾微粒体代谢以及肠道代谢进行研究。在体内，14R-OTA的血浆浓度将根据含有14R-OTA的食物样本的摄入量进行筛选，特别是咖啡。为了进一步查明14R-OTA暴露的来源，将对相关食品类别进行分析，主要集中在热处理样品上。根据获得的关于14R-OTA的发生、代谢和生物利用度的数据，将评估14R-OTA对消费者的毒理学相关性。

Various chemical reactions are responsible for the degradation of the mycotoxin Ochratoxin A (OTA) during thermal food processing, e.g. during roasting of coffee or extrusion cooking of grain. In the first funding period we could show for the first time that besides the isomerization of OTA to 14R-ochratoxin A (14R-OTA) a covalent matrix-binding of OTA to polysaccharides occurs. Furthermore we could show that these matrix-bound forms are cleaved either during the brewing of coffee or during the intestinal metabolism leading to the release of OTA. In addition to the first funding period we analyzed blood samples of coffee and non-coffee drinkers for the occurrence of OTA and 14R-OTA. We could show that 14R-OTA is detectable in relatively high levels in blood samples in some cases with even higher levels compared to OTA. In the following proposal the reasons for these high levels will be studied. For this in vitro studies for mechanistic evaluations as well as in vivo studies with humans are planned. During the in vitro experiments the binding to plasma proteins, the metabolism in liver and kidney microsomes as well as the intestinal metabolism using the pig-cecum-model will be studied in comparison of OTA and 14R-OTA. In vivo the plasma concentration of 14R-OTA will be screened depending on the consumption of 14R-OTA-containing food samples, especially coffee. In order to detect further sources for 14R-OTA exposure, relevant food groups will be analyzed with the main focus on thermal processed samples.With the obtained data concerning occurrence, metabolism and bioavailability of 14R-OTA the toxicological relevance for the consumer will be evaluated.