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人类对有机磷农药引起的神经退行性和神经发育毒性的易感性。

The susceptibility of humans to neurodegenerative and neurodevelopmental toxicities caused by organophosphorus pesticides.

机构信息

Department of Pharmacology & Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Arch Toxicol. 2023 Dec;97(12):3037-3060. doi: 10.1007/s00204-023-03604-2. Epub 2023 Oct 3.

Abstract

The toxicology field is concerned with the impact of organophosphorus (OP) compounds on human health. These compounds have been linked to an increased risk of neurological disorders, including neurodegenerative and neurodevelopmental diseases. This article aims to review studies on the role of OP compounds in developing these neurological disorders and explore how genetic variations can affect susceptibility to the neurotoxicity of these pesticides. Studies have shown that exposure to OP compounds can lead to the development of various neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD), autism, intellectual disability, and other developmental neurotoxicities. Apart from inhibiting the cholinesterase enzyme, OP compounds are believed to cause other pathological mechanisms at both the extracellular level (cholinergic, serotonergic, dopaminergic, glutamatergic, and GABAergic synapses) and the intracellular level (oxidative stress, mitochondrial dysfunction, inflammation, autophagy, and apoptosis) that contribute to these disorders. Specific genetic polymorphisms, including PON1, ABCB1, NOS, DRD4, GST, CYP, and APOE, have increased the risk of developing OP-related neurological disorders.

摘要

毒理学领域关注有机磷 (OP) 化合物对人类健康的影响。这些化合物与神经紊乱风险增加有关,包括神经退行性和神经发育性疾病。本文旨在综述研究 OP 化合物在这些神经紊乱发展中的作用,并探讨遗传变异如何影响对这些杀虫剂神经毒性的易感性。研究表明,接触 OP 化合物可导致各种神经紊乱的发生,如阿尔茨海默病 (AD)、帕金森病 (PD)、注意缺陷多动障碍 (ADHD)、自闭症、智力障碍和其他发育神经毒性。除了抑制胆碱酯酶,OP 化合物还被认为在外周水平(胆碱能、5-羟色胺能、多巴胺能、谷氨酸能和 GABA 能突触)和细胞内水平(氧化应激、线粒体功能障碍、炎症、自噬和细胞凋亡)引起其他病理机制,这些机制有助于这些疾病的发生。特定的遗传多态性,包括 PON1、ABCB1、NOS、DRD4、GST、CYP 和 APOE,增加了患 OP 相关神经紊乱的风险。

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