¹H NMR 研究野百合碱及其在人血中的代谢物。

¹H NMR study of monocrotaline and its metabolites in human blood.

机构信息

Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.

出版信息

Food Chem Toxicol. 2011 Nov;49(11):2793-9. doi: 10.1016/j.fct.2011.07.063. Epub 2011 Aug 6.

DOI:10.1016/j.fct.2011.07.063

Abstract

Monocrotaline (MCT) is a naturally occurring hepatotoxic pyrrolizidine alkaloid found in plants. This investigation is aimed at furthering the understanding of the role of blood in mediating the transport of MCT and its reactive metabolites in humans. Reactions of monocrotaline and its metabolites, dehydromonocrotaline (DHM), retronecine (RET) and dehydroretronecine (DHR) with human blood plasma, red blood cells (RBCs), and whole blood were studied in vitro by proton nuclear magnetic resonance spectroscopy. In plasma MCT remained intact and weakly associated with plasma proteins, and DHM was rapidly hydrolyzed releasing necic and lactone acids, and the reactive pyrrolic metabolite. MCT and its metabolite DHM were internalized in RBCs to the extent of 46.0% and 48.9% respectively in 30 min. No polymerization of DHR was observed when incubated with plasma and RBCs. The data clearly showed that both human plasma and RBCs could be the carriers for the transportation of MCT and its metabolites, DHM, RET and DHR between organs and could stabilise the reactive MCT metabolite DHR.

摘要

野百合碱（MCT）是一种天然存在的肝毒性吡咯里西啶生物碱，存在于植物中。本研究旨在进一步了解血液在介导 MCT 及其反应性代谢物在人体内的转运中的作用。通过质子核磁共振波谱法研究了野百合碱及其代谢物脱水野百合碱（DHM）、 retronecine（RET）和去氢 retronecine（DHR）与人体血浆、红细胞（RBC）和全血的体外反应。在血浆中，MCT 保持完整且与血浆蛋白弱结合，DHM 迅速水解释放 necic 和内酯酸以及反应性吡咯代谢物。MCT 和其代谢物 DHM 在 30 分钟内分别以 46.0%和 48.9%的程度被内化到 RBC 中。当与血浆和 RBC 孵育时，未观察到 DHR 的聚合。数据清楚地表明，人血浆和 RBC 都可以作为 MCT 及其代谢物、DHM、RET 和 DHR 在器官之间运输的载体，并可以稳定反应性 MCT 代谢物 DHR。