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谷胱甘肽过氧化物酶4/ Toll样受体4信号通路的激活参与了硒酵母对鹌鹑溴氰菊酯诱发脑损伤的缓解作用。

Activation of the GPX4/TLR4 Signaling Pathway Participates in the Alleviation of Selenium Yeast on Deltamethrin-Provoked Cerebrum Injury in Quails.

作者信息

Li Jiayi, Yu Zhongxian, Han Bing, Li Siyu, Lv Yueying, Wang Xiaoqiao, Yang Qingyue, Wu Pengfei, Liao Yuge, Qu Bing, Zhang Zhigang

机构信息

College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.

Pharmacy Department, The Affiliated Hospital To Changchun University of Chinese Medicine, 1478 Gongnong Road, Hongqi Street, Chaoyang District, Changchun, Jilin Province, 130021, China.

出版信息

Mol Neurobiol. 2022 May;59(5):2946-2961. doi: 10.1007/s12035-022-02744-3. Epub 2022 Mar 5.

DOI:10.1007/s12035-022-02744-3
PMID:35247140
Abstract

Deltamethrin (DLM) is a member of pyrethroid pesticide widely applied for agriculture and aquaculture, and its residue in the environment seriously threatens the bio-safety. The cerebrum might be vulnerable to pesticide-triggered oxidative stress. However, there is no specific antidote for treating DLM-triggered cerebral injury. Selenium (Se) is an essential trace element functionally forming selenoprotein glutathione peroxidase (GPX) in antioxidant defense. Se yeast (SY) is a common and effective organic form of Se supplement with high selenomethionine content. Accordingly, this study focused on investigating the therapeutic potential of SY on DLM-induced cerebral injury in quails after chronically exposing to DLM and exploring the underlying mechanisms. Quails were treated with/without SY (0.4 mg kg SY added in standard diet) in the presence/absence of DLM (45 mg kg body weight intragastrically) for 12 weeks. The results showed SY supplementation ameliorated DLM-induced cerebral toxicity. Concretely, SY elevated the content of Se and increased GPX4 level in DLM-treated quail cerebrum. Furthermore, SY enhanced antioxidant defense system by upregulating nuclear factor-erythroid-2-related factor 2 (Nrf2) associated members. Inversely, SY diminished the changes of apoptosis- and inflammation-associated proteins and genes including toll-like receptor 4 (TLR4). Collectively, our results suggest that dietary SY protects against DLM-induced cerebral toxicity in quails via positively regulating the GPX4/TLR4 signaling pathway. GPX4 may be a potential therapeutic target for insecticide-induced biotoxicity.

摘要

溴氰菊酯(DLM)是一种广泛应用于农业和水产养殖的拟除虫菊酯类农药,其在环境中的残留严重威胁生物安全。大脑可能易受农药引发的氧化应激影响。然而,目前尚无治疗DLM引发脑损伤的特效解毒剂。硒(Se)是一种必需微量元素,在抗氧化防御中可功能性地形成硒蛋白谷胱甘肽过氧化物酶(GPX)。硒酵母(SY)是一种常见且有效的有机硒补充剂,富含高含量的硒代蛋氨酸。因此,本研究聚焦于探究SY对长期暴露于DLM后的鹌鹑DLM诱导脑损伤的治疗潜力,并探索其潜在机制。鹌鹑在有/无DLM(45mg/kg体重灌胃)的情况下,接受/不接受SY(标准日粮中添加0.4mg/kg SY)处理12周。结果表明,补充SY可改善DLM诱导的脑毒性。具体而言,SY提高了DLM处理的鹌鹑大脑中Se的含量并增加了GPX4水平。此外,SY通过上调核因子红系2相关因子2(Nrf2)相关成员增强了抗氧化防御系统。相反,SY减少了包括Toll样受体4(TLR4)在内的凋亡和炎症相关蛋白及基因的变化。总体而言,我们的结果表明,日粮中的SY通过正向调节GPX4/TLR4信号通路,保护鹌鹑免受DLM诱导的脑毒性。GPX4可能是杀虫剂诱导生物毒性的潜在治疗靶点。

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