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噻虫嗪通过调节 Nrf2/NF-κB/iNOS 信号通路和炎症细胞因子诱导雄性大鼠神经氧化应激:水飞蓟素的神经保护作用。

Thiamethoxam evoked neural oxido-inflammatory stress in male rats through modulation of Nrf2/NF-kB/iNOS signaling and inflammatory cytokines: Neuroprotective effect of Silymarin.

机构信息

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.

Department of Animal Husbandry and Wealth Development Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.

出版信息

Neurotoxicology. 2023 May;96:28-36. doi: 10.1016/j.neuro.2023.03.004. Epub 2023 Mar 22.

DOI:10.1016/j.neuro.2023.03.004
PMID:36958429
Abstract

Thiamethoxam (TMX), a neonicotinoid insecticide, is a widely used insecticide with neurotoxic potential. Silymarin (SM), a milk thistle-derived flavonoid, is known with its promising biological activities. This study explored the neuroprotective effects of SM against TMX-triggered cortical injury in male rats. Animals were divided into four groups and treated daily either with SM (150 mg/kg), TMX (78.15 mg/kg), or both at the aforementioned doses for 28 days. Our results revealed marked declines in cortical SOD and CAT activities with elevations in MDA, IL-1b and TNF-α levels in TMX-treated rats. Further, TMX induced down-regulation in the gene expressions of Sod, Cat, Gpx, and Nrf-2, with up-regulation in the gene expressions of IL-1b, IL-6, iNOS, TNF-α and NF-kB. Interestingly, pre-treatment with SM provided a notable neuroprotective action against TMX-mediated cortical damage that indicates its promising antioxidant and anti-inflammatory activities. This effect may be mediated by Nrf2/NF-kB/iNOS signalling and suppression of excess free radicals and production of inflammatory cytokines. In brief, SM could be a promising therapeutic agent against TMX-mediated neural complication via its antioxidant and anti-inflammatory properties. PRACTICAL APPLICATIONS: The using of neonicotinoids as thiamethoxam is recently increased and is associated with brain damage. TMX induced excessive oxidative and inflammatory damage. Therefore, new therapeutic approaches are needed to counteract its adverse effects on the nervous system. SM, a flavonoid, is extracted from the seeds and fruits of milk thistle. Due to its potent antioxidative activity, SM have been applied to mitigate the oxidative stress as well as inflammatory disorders. Herein, we examined the potential therapeutic role of SM against TMX-induced brain oxidative stress and inflammation in rats through evaluating oxidative markers, inflammatory response, and histopathological changes in the brain cortical tissue.

摘要

噻虫嗪(TMX)是一种新烟碱类杀虫剂,具有潜在的神经毒性。水飞蓟素(SM)是一种来源于奶蓟草的类黄酮,具有多种有前景的生物学活性。本研究旨在探讨 SM 对 TMX 诱发的雄性大鼠皮质损伤的神经保护作用。动物被分为四组,每天分别用 SM(150mg/kg)、TMX(78.15mg/kg)或上述两种药物以所述剂量治疗 28 天。我们的结果显示,TMX 处理组大鼠皮质 SOD 和 CAT 活性明显下降,MDA、IL-1b 和 TNF-α 水平升高。此外,TMX 还诱导 Sod、Cat、Gpx 和 Nrf-2 基因表达下调,以及 Il-1b、Il-6、iNOS、TNF-α 和 NF-kB 基因表达上调。有趣的是,SM 预处理对 TMX 介导的皮质损伤具有显著的神经保护作用,表明其具有抗氧化和抗炎作用。这种作用可能是通过 Nrf2/NF-kB/iNOS 信号通路和抑制过量自由基和炎症细胞因子的产生来介导的。总之,SM 可能通过其抗氧化和抗炎特性成为一种有前途的治疗 TMX 介导的神经并发症的药物。 实际应用:新烟碱类杀虫剂,如噻虫嗪的使用最近有所增加,并且与脑损伤有关。TMX 诱导过度的氧化和炎症损伤。因此,需要新的治疗方法来对抗其对神经系统的不良影响。SM 是一种从奶蓟草的种子和果实中提取的类黄酮。由于其强大的抗氧化活性,SM 已被用于减轻氧化应激和炎症性疾病。在这里,我们通过评估大脑皮质组织中的氧化标志物、炎症反应和组织病理学变化,研究了 SM 对 TMX 诱导的大鼠大脑氧化应激和炎症的潜在治疗作用。

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