Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos.

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Hong-Ling Zhou, Bei-Bei Wang, Xu-Li Fan, Xiao-Min Zhang, Ying Song
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引用次数: 0

Abstract

This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague-Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative injury model using CPF, and the protective effects and mechanism of action of CAA against CPF-induced oxidative damage were explored in vitro. The key role of Nuclear factor erythroid-2-related factor 2 (Nrf2) in alleviating CPF-induced damage via CAA was further confirmed by administering Nrf2 inhibitors to PC12 cells. Administration of CAA significantly enhanced the locomotor ability of the rats, alleviated neuronal pathological alterations, and increased the number of Nissl bodies, while increasing autophagic bodies. In vitro, CAA promoted cell survival and augmented the mitochondrial membrane potential. It decreased both intra- and extracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), while markedly elevating mitochondrial DNA (mtDNA) copy number. Moreover, PC12 cells treated with Nrf2 inhibitors failed to exhibit any improvement in survival rate when treated with CAA after a toxic insult. Furthermore, ROS and MDA levels were not significantly reduced, SOD enzyme activity did not increase, and mitochondrial membrane potential and mtDNA copy number did not improve. Western blot analysis showed that the expression of Tfam, Beclin1, and LC3II/LC3I proteins in the CAA group decreased significantly after Nrf2 inhibition. These findings suggest that CAA modulates mitochondrial function and autophagy by regulating the Nrf2 signalling pathway to mitigate the toxic damage. Finally, the effect of the autophagy inhibitor, 3-MA, on PC12 cells suggests that CAA promotes mitophagy by participating in the Nrf2 pathway, thereby preventing CPF-induced oxidative stress damage.

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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
期刊介绍: Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.
文献相关原料
公司名称 产品信息 采购帮参考价格
阿拉丁 Chlorpyrifos
阿拉丁 Pralidoxime
阿拉丁 Pralidoxime
阿拉丁 Edaravone
阿拉丁 Edaravone
阿拉丁 Chlorpyrifos
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