Oyovwi Mega Obukohwo, Atere Adedeji David, Chimwuba Paul, Joseph Uchechukwu Gregory
Department of Physiology, Faculty of Basic Medical Sciences, Adeleke University, Ede, Osun State, Nigeria.
Department of Medical Laboratory Science, College of Health Sciences, Osun State University, Osogbo, Nigeria.
Neurotox Res. 2024 Dec 16;43(1):1. doi: 10.1007/s12640-024-00723-1.
Pyrethroids, synthetic insecticides used in pest management, pose health risks, particularly neurotoxic effects, with studies linking exposure to a neurodegenerative disorder. This review examines the neurotoxic mechanisms of pyrethroids analyzing literature from animal model studies. It identifies critical targets for neurotoxicity, including ion channels, oxidative stress, inflammation, neuronal cell loss, and mitochondrial dysfunction. The review also discusses key therapeutic targets and signaling pathways relevant to Pyrethroids neurotoxicity management, including calcium, Wnt/β-catenin, mTOR, MAPK/Erk, PI3K/Akt, Nrf2, Nurr1, and PPARγ. Our findings demonstrate that pyrethroid exposure triggers multiple neurotoxic pathways that bear resemblance to the mechanisms underlying neurotoxicity. Oxidative stress and inflammation emerge as prominent factors that contribute to neuronal degeneration, alongside disrupted mitochondrial function. The investigation highlights the significance of ion channels as primary neurodegeneration targets while acknowledging the potential involvement of various other receptors and enzymes that may exacerbate neurological damage. Additionally, we elucidate how pyrethroids may interfere with therapeutic targets associated with neuronal dysfunction, potentially impairing treatment efficacy.Also, exposure to these chemicals can alter DNA methylation patterns and histone modifications, ultimately leading to changes in gene expression that may enhance susceptibility to neurological disorders. Pyrethroid neurotoxicity poses a significant public health risk, necessitating future research for protective strategies against pesticide-induced neurological disorders and understanding the interplay between neurodegenerative diseases, potentially leading to innovative therapeutic interventions.
拟除虫菊酯是用于害虫治理的合成杀虫剂,会带来健康风险,尤其是神经毒性作用,有研究将其暴露与一种神经退行性疾病联系起来。本综述通过分析动物模型研究的文献,探讨了拟除虫菊酯的神经毒性机制。它确定了神经毒性的关键靶点,包括离子通道、氧化应激、炎症、神经元细胞丢失和线粒体功能障碍。该综述还讨论了与拟除虫菊酯神经毒性管理相关的关键治疗靶点和信号通路,包括钙、Wnt/β-连环蛋白、mTOR、MAPK/Erk、PI3K/Akt、Nrf2、Nurr1和PPARγ。我们的研究结果表明,拟除虫菊酯暴露会触发多种神经毒性途径,这些途径与神经毒性的潜在机制相似。氧化应激和炎症是导致神经元变性的突出因素,同时伴有线粒体功能紊乱。该调查强调了离子通道作为主要神经退行性变靶点的重要性,同时也认识到其他各种可能加剧神经损伤的受体和酶的潜在作用。此外,我们还阐明了拟除虫菊酯如何干扰与神经元功能障碍相关的治疗靶点,可能会削弱治疗效果。此外,接触这些化学物质会改变DNA甲基化模式和组蛋白修饰,最终导致基因表达变化,可能会增加对神经疾病的易感性。拟除虫菊酯神经毒性构成了重大的公共卫生风险,需要未来开展研究以制定针对农药诱导的神经疾病的保护策略,并了解神经退行性疾病之间的相互作用,这可能会带来创新的治疗干预措施。