Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders
Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders
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DOI：
10.1021/acs.chemrestox.6b00310
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发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Burcham, Philip C.
中科院分区：
文献类型：
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作者：
Burcham, Philip C.
丙烯醛是一种参与许多疾病的高毒性亲电体，然而，由于其在人类环境中的广泛分布，描述其对特定条件的精确机制贡献的努力变得复杂。该观点提出，由于其作为环境污染物、代谢副产物和通过普遍存在的病理生理过程形成的内毒素的混合状态，许多疾病可能涉及从多种来源释放的丙烯醛。虽然类别界限不明确，但至少有四种可识别的暴露情景是可识别的。首先，在某些综合征中，如伴随慢性或急性烟雾中毒的综合征，丙烯醛在疾病发病机制中所起的任何作用主要追溯到外源性来源，如烟草或其他有机物质的燃烧。第二类接触涉及在体内经历代谢以释放丙烯醛的异生物质。然而，还有其他健康状况涉及通过几种内源性途径形成的丙烯醛，其中一些在与异生物质中毒时被激活（即，暴露类别3），而还有一些则伴随着对身体组织的直接物理创伤（暴露类别4）。澄清内源性丙烯醛在人类疾病中的作用的进一步复杂化的努力是，许多这样的综合征是复杂的现象，类似于“化学混合物暴露”，同时涉及多种有毒物质。这一观点认为，虽然近几十年来在描述丙烯醛在细胞和分子水平上的有害影响方面取得了很大进展，但还需要更多的工作来确定不同丙烯醛来源对人类受试者“真实世界”健康状况的贡献。
Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.