Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.
Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.
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DOI：
10.1111/jnc.14077
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发表时间：
2017-08
影响因子：
4.7
通讯作者：
Albuquerque EX
中科院分区：
文献类型：
--
作者：
Burke RD;Todd SW;Lumsden E;Mullins RJ;Mamczarz J;Fawcett WP;Gullapalli RP;Randall WR;Pereira EFR;Albuquerque EX
有机磷（OP）杀虫剂是全世界广泛使用的害虫控制剂。不幸的是，它们也因其可能在人类中引发的毒性作用而闻名。人类急性接触OP杀虫剂的临床表现包括明确的胆碱能危象，这是由于乙酰胆碱酯酶（AChE）（水解神经递质乙酰胆碱（ACh）的酶）的不可逆抑制而发生的。长期暴露于不足以引发急性中毒迹象的OP杀虫剂水平（以下称为亚急性暴露）也与神经功能障碍有关。特别是，流行病学研究报告称，产前亚急性接触有机磷杀虫剂（包括毒死蜱）与儿童期从认知障碍到震颤的神经缺陷之间存在统计学显著相关性。本文的主要目的是：（一）解决与人类急性和亚急性暴露于OP杀虫剂相关的短期和长期神经问题，特别是在生命早期;（二）讨论OP杀虫剂发育暴露动物模型的翻译相关性;（三）审查可能导致OP杀虫剂发育神经毒性的机制。大部分讨论将集中在毒死蜱，在美国和世界各地最畅销的有机磷杀虫剂。这些要点对于识别和开发安全有效的干预措施以对抗和/或预防这些化学品在发育中的大脑中的神经毒性作用至关重要。
Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain.
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