Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning, People's Republic of China.
J Ethnopharmacol. 2022 Jan 10;282:114582. doi: 10.1016/j.jep.2021.114582. Epub 2021 Sep 4.
Due to the modernization of traditional Chinese medicine (TCM) and the influence of traditional medication habits (TCM has no toxicity or side effects), arsenic poisoning incidents caused by the abuse of realgar and realgar-containing Chinese patent medicines have occurred occasionally. However, the potential mechanism of central nervous system toxicity of realgar remains unclear.
This study aimed to clarify the specific mechanism of realgar-induced neurotoxicity.
In this study, the roles of ERK1/2 and p38 MAPK in realgar-induced neuronal autophagy and overactivation of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) signalling pathways was investigated in vivo and in vitro.
The arsenic in realgar passed through the blood-brain barrier and accumulated in the brain, resulting in damage to neurons, synapses and myelin sheaths in the cerebral cortex and a decrease in the total antioxidant capacity. The specific mechanism is that the excessive activation of Nrf2 is regulated by the upstream signalling molecules ERK1/2 and p38MAPK. At the same time, p38 MAPK and ERK1/2 interfere with autophagy, thereby promoting autophagy initiation but causing subsequent dysfunctional autophagic degradation and inducing the p62-Keap1-Nrf2 feedback loop to promote Nrf2 signalling pathway activation and nerve cell apoptosis.
This study confirmed the role of the signalling molecules p38 MAPK and ERK1/2 in perturbing autophagy and inducing the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway in realgar-induced neurotoxicity.
由于中药现代化和传统用药习惯（中药无毒副作用）的影响，偶尔会发生因滥用雄黄和含雄黄的中成药而导致砷中毒的事件。然而，雄黄致中枢神经系统毒性的潜在机制尚不清楚。
本研究旨在阐明雄黄诱导神经毒性的具体机制。
在这项研究中，体内和体外研究了 ERK1/2 和 p38 MAPK 在雄黄诱导的神经元自噬和核因子红细胞衍生 2 相关因子（Nrf2）信号通路过度激活中的作用。
结果表明，雄黄中的砷穿过血脑屏障并在大脑中蓄积，导致大脑皮质神经元、突触和髓鞘损伤，总抗氧化能力降低。具体机制是，Nrf2 的过度激活受上游信号分子 ERK1/2 和 p38MAPK 的调节。同时，p38 MAPK 和 ERK1/2 干扰自噬，从而促进自噬的起始，但导致随后的功能失调的自噬降解，并诱导 p62-Keap1-Nrf2 反馈环，以促进 Nrf2 信号通路的激活和神经细胞凋亡。
本研究证实了信号分子 p38 MAPK 和 ERK1/2 在干扰自噬和诱导 p62-Keap1-Nrf2 反馈环以激活雄黄诱导的神经毒性中的 Nrf2 信号通路中的作用。
