Profiling the reactive metabolites of xenobiotics using metabolomic technologies.
Profiling the reactive metabolites of xenobiotics using metabolomic technologies.
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DOI：
10.1021/tx200033v
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发表时间：
2011-05-16
影响因子：
4.1
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Li F;Lu J;Ma X
外源性物质引起的毒性的主要途径是由生物活化引发的。表征反应中间体将提供有关反应物质结构的信息，从而定义潜在的生物活化机制。由于大多数反应性代谢物不稳定，因此很难直接检测它们。反应性代谢物可以与捕获试剂（例如谷胱甘肽）形成加合物，从而使反应性代谢物可被检测到。然而，从复杂的生物基质中“捞出”这些加合物具有挑战性，特别是对于通过不常见的代谢途径产生的加合物。在这方面，我们开发了一种基于代谢组学技术的新方法来筛选捕获的反应性代谢物。使用这种代谢组学方法重新检查了胡薄荷酮、对乙酰氨基酚和氯氮平的生物活性。在所有这些情况下，很容易识别出大量被捕获的反应性代谢物。这些数据表明，这种代谢组学方法是分析外源生物活性的有效工具。
A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them directly. Reactive metabolites can form adducts with trapping reagents, such as glutathione, which makes the reactive metabolites detectable. However, it is challenging to “fish” these adducts out from a complex biological matrix, especially for adducts generated via uncommon metabolic pathways. In this regard, we developed a novel approach based upon metabolomic technologies to screen trapped reactive metabolites. The bioactivation of pulegone, acetaminophen, and clozapine were reexamined by using this metabolomic approach. In all these cases, a large number of trapped reactive metabolites were readily identified. These data indicate that this metabolomic approach is an efficient tool to profile xenobiotic bioactivation.