Department of Pathology, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt.
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Neurochem Res. 2022 Oct;47(10):3051-3062. doi: 10.1007/s11064-022-03654-5. Epub 2022 Jun 30.
Pesticides are widely used in agriculture to kill pests, but their action is non-selective and results in several hazardous effects on humans and animals. Pesticide toxicity has been demonstrated to alter a variety of neurological functions and predisposes to various neurodegenerative diseases. Although, there is no data available for hexaflumuron (HFM) and hymexazol (HML) neurotoxicity. Hence, the present study aims to investigate the possible mechanisms of HFM and HML neurotoxicity. 21 male Wistar rats were divided into three groups and daily received the treatment via oral gavage for 14 days as follows: group (1) normal saline, group (2) HFM (1/100LD50), and group (3) HML (1/100 LD50). Our results revealed that both HFM and HML produced a significant increase in MDA levels and a decrease in GSH and CAT activity in some brain areas. There were severe histopathological alterations mainly neuronal necrosis and gliosis in different examined areas. Upregulation of mRNA levels of JNK and Bax with downregulation of Bcl-2 was also recorded in both pesticides exposed groups. In all studied toxicological parameters, HML produced neurotoxicity more than HFM. HFM targets the cerebral cortex and striatum, while HML targets the cerebral cortex, striatum, hippocampus, and cerebellum. We can conclude that both HFM and HML provoke neurobehavioral toxicity through oxidative stress that impairs the mitochondrial function and activates the JNK-dependent apoptosis pathway.
农药在农业中被广泛用于杀死害虫，但它们的作用是非选择性的，会对人类和动物造成多种危险影响。已证明农药毒性会改变多种神经功能，并导致各种神经退行性疾病。虽然目前尚无关于六氟菊酯（HFM）和四螨嗪（HML）神经毒性的数据。因此，本研究旨在探讨 HFM 和 HML 神经毒性的可能机制。21 只雄性 Wistar 大鼠分为三组，每天通过口服灌胃接受 14 天的治疗，如下所示：组（1）生理盐水，组（2）HFM（1/100LD50）和组（3）HML（1/100 LD50）。我们的结果表明，HFM 和 HML 均可显著增加某些脑区的 MDA 水平，降低 GSH 和 CAT 活性。在不同检查区域均观察到严重的组织病理学改变，主要为神经元坏死和神经胶质增生。两种农药暴露组还记录到 JNK 和 Bax 的 mRNA 水平上调以及 Bcl-2 的下调。在所有研究的毒理学参数中，HML 引起的神经毒性大于 HFM。HFM 靶向大脑皮层和纹状体，而 HML 靶向大脑皮层、纹状体、海马体和小脑。我们可以得出结论，HFM 和 HML 均通过氧化应激引发神经行为毒性，从而损害线粒体功能并激活依赖 JNK 的细胞凋亡途径。
