Department of Molecular Biosciences, UC Davis School of Veterinary Medicine, One Shields Ave., Davis, CA 95616, USA.
Neurotoxicology. 2012 Jun;33(3):575-84. doi: 10.1016/j.neuro.2012.02.002. Epub 2012 Feb 10.
Organophosphorus (OP) nerve agents and pesticides inhibit acetylcholinesterase (AChE), and this is thought to be a primary mechanism mediating the neurotoxicity of these compounds. However, a number of observations suggest that mechanisms other than or in addition to AChE inhibition contribute to OP neurotoxicity. There is significant experimental evidence that acute OP intoxication elicits a robust inflammatory response, and emerging evidence suggests that chronic repeated low-level OP exposure also upregulates inflammatory mediators. A critical question that is just beginning to be addressed experimentally is the pathophysiologic relevance of inflammation in either acute or chronic OP intoxication. The goal of this article is to provide a brief review of the current status of our knowledge linking inflammation to OP intoxication, and to discuss the implications of these findings in the context of therapeutic and diagnostic approaches to OP neurotoxicity.
有机磷(OP)神经毒剂和农药抑制乙酰胆碱酯酶(AChE),这被认为是介导这些化合物神经毒性的主要机制。然而,许多观察结果表明,除了 AChE 抑制之外,还有其他机制参与了 OP 神经毒性。有大量实验证据表明,急性 OP 中毒会引发强烈的炎症反应,新出现的证据表明,慢性重复低水平 OP 暴露也会上调炎症介质。一个刚刚开始通过实验解决的关键问题是炎症在急性或慢性 OP 中毒中的病理生理相关性。本文的目的是简要回顾目前我们对炎症与 OP 中毒之间联系的认识,并讨论这些发现对 OP 神经毒性的治疗和诊断方法的意义。