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芝麻油对大鼠锰诱导的帕金森样疾病的保护作用。

The protective role of sesame oil against Parkinson's-like disease induced by manganese in rats.

作者信息

Sarawi Wedad S, Attia Hala A, Alomar Hatun A, Alhaidar Rawan, Rihan Esraa, Aldurgham Nora, Ali Rehab A

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.

出版信息

Behav Brain Res. 2024 May 8;465:114969. doi: 10.1016/j.bbr.2024.114969. Epub 2024 Mar 26.

Abstract

Chronic exposure to manganese (Mn) results in motor dysfunction, biochemical and pathological alterations in the brain. Oxidative stress, inflammation, and dysfunction of dopaminergic and GABAergic systems stimulate activating transcription factor-6 (ATF-6) and protein kinase RNA-like ER kinase (PERK) leading to apoptosis. This study aimed to investigate the protective effect of sesame oil (SO) against Mn-induced neurotoxicity. Rats received 25 mg/kg MnCl and were concomitantly treated with 2.5, 5, or 8 ml/kg of SO for 5 weeks. Mn-induced motor dysfunction was indicated by significant decreases in the time taken by rats to fall during the rotarod test and in the number of movements observed during the open field test. Also, Mn resulted in neuronal degeneration as observed by histological staining. The striatal levels of lipid peroxides and reduced glutathione (oxidative stress markers), interleukin-6 and tumor necrosis factor-α (inflammatory markers) were significantly elevated. Mn significantly reduced the levels of dopamine and Bcl-2, while GABA, PERK, ATF-6, Bax, and caspase-3 were increased. Interestingly, all SO doses, especially at 8 ml/kg, significantly improved locomotor activity, biochemical deviations and reduced neuronal degeneration. In conclusion, SO may provide potential therapeutic benefits in enhancing motor performance and promoting neuronal survival in individuals highly exposed to Mn.

摘要

长期接触锰(Mn)会导致运动功能障碍以及大脑中的生化和病理改变。氧化应激、炎症以及多巴胺能和γ-氨基丁酸能系统功能障碍会刺激激活转录因子6(ATF-6)和蛋白激酶RNA样内质网激酶(PERK),从而导致细胞凋亡。本研究旨在探讨芝麻油(SO)对锰诱导的神经毒性的保护作用。大鼠接受25mg/kg的氯化锰,并同时分别用2.5、5或8ml/kg的芝麻油处理5周。在转棒试验中,大鼠跌落所需时间显著减少,在旷场试验中观察到的运动次数显著减少,这表明锰诱导了运动功能障碍。此外,组织学染色显示锰导致了神经元变性。纹状体中脂质过氧化物和还原型谷胱甘肽(氧化应激标志物)、白细胞介素-6和肿瘤坏死因子-α(炎症标志物)的水平显著升高。锰显著降低了多巴胺和Bcl-2的水平,而γ-氨基丁酸、PERK、ATF-6、Bax和半胱天冬酶-3的水平则升高。有趣的是,所有剂量的芝麻油,尤其是8ml/kg时,均显著改善了运动活性、生化指标偏差,并减少了神经元变性。总之,芝麻油可能为高暴露于锰的个体增强运动能力和促进神经元存活提供潜在的治疗益处。

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