Neurotoxicity mechanisms of pyrethroids studied by network toxicology and molecular docking.

IF 2.7 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics
Yuting Lin, Wenqi Zeng, Yang Zhang, Yanghui Hu, Zhonghan Liang, Zhixing Chen, Zhuoying Lu, Weien Zhang, Zhenjie Wang, Yanling Jiang, Mingyu Chen, Haining Ma, Yikuan Du, Chunling Ma, Chun Yang
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引用次数: 0

Abstract

Pyrethroids (PYs), a class of insecticides widely used in agricultural and household pest control, have been reported to trigger neurological damage. However, the underlying mechanisms of toxicity remain unclear. In this study, we applied a network toxicology approach to identify the core targets and signaling pathways associated with the pathogenesis of PYs-induced neurotoxicity syndrome. A molecular docking approach was also used to determine the interactions between PYs and key proteins. In this study, 145 potential targets and 10 core targets of PYs-induced neurotoxicity were identified. The core targets included SRC, EGFR, and KDR, and the signaling pathways involved Prolactin signaling pathway, AGE-RAGE signaling pathway in diabetic complications and Lipid and atherosclerosis. Molecular docking binding showed stable binding of PYs to core targets. This study preliminarily reveals the potential toxicity and possible neurotoxicity mechanism of pyrethroids, which provides new ideas for subsequent prevention and treatment of related diseases.

网络毒理学与分子对接研究拟除虫菊酯的神经毒性机制。
拟除虫菊酯(pyys)是一种广泛用于农业和家庭害虫防治的杀虫剂,据报道会引起神经损伤。然而,潜在的毒性机制仍不清楚。在这项研究中,我们应用网络毒理学方法来确定与pys诱导的神经毒性综合征发病机制相关的核心靶点和信号通路。分子对接方法也用于确定PYs与关键蛋白之间的相互作用。本研究共鉴定出145个潜在靶点和10个核心靶点。核心靶点包括SRC、EGFR和KDR,信号通路涉及糖尿病并发症中的催乳素信号通路、AGE-RAGE信号通路以及脂质和动脉粥样硬化。分子对接结合显示PYs与核心靶点的稳定结合。本研究初步揭示了拟除虫菊酯的潜在毒性和可能的神经毒性机制,为后续相关疾病的防治提供了新的思路。
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来源期刊
CiteScore
6.60
自引率
3.10%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.
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