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姜黄素可减轻三氧化二砷诱导的小鼠纹状体区域神经损伤。

Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.

作者信息

Pandey Kamlesh Kumar, Mehta Kamakshi, Kaur Balpreet, Dhar Pushpa

机构信息

Department of Anatomy, All India Institute of Medical Sciences, New Delhi, 110029, India.

Department of Ophthalmology, University of Pittsburgh School of Medicine, UPMC Vision Institute, Pittsburgh, PA, 15219, USA.

出版信息

Psychopharmacology (Berl). 2025 Mar;242(3):497-520. doi: 10.1007/s00213-024-06700-y. Epub 2024 Oct 23.

Abstract

RATIONALE

Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (AsO) in the mouse striatal region.

METHODS

Healthy adult male mice were chronically administered with varying concentrations of AsO (2, 4 and 8 mg/kg bw) alone and along with CUR (100 mg/kg bw) orally for 45 days. Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations.

RESULTS

Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to AsO compared to controls. Simultaneous treatment of AsO (2, 4 and 8 mg/kg bw) and curcumin (100 mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. AsO alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of AsO (4 and 8 mg/kg bw). However, these changes were reversed in mice who received AsO + CUR co-treatment.

CONCLUSIONS

Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against AsO-induced behavioral deficits, as well as biochemical and morphological alterations.

摘要

理论依据

砷诱导的神经毒性具有剂量依赖性效应,在啮齿动物中已有充分记录。姜黄素(CUR)是一种经济高效的植物多酚,通过调节氧化应激、细胞凋亡和神经化学发挥神经保护作用。本研究评估姜黄素对小鼠纹状体区域三氧化二砷(AsO)的神经保护潜力。

方法

健康成年雄性小鼠单独或与姜黄素(100mg/kg体重)一起口服不同浓度的AsO(2、4和8mg/kg体重),持续45天。在实验期结束时,对动物进行行为范式测试,包括旷场试验、新物体识别、转棒试验和莫里斯水迷宫试验。在第46天从动物身上新鲜采集纹状体组织进行生化分析(丙二醛、谷胱甘肽过氧化物酶和谷胱甘肽)。此外,对灌注固定的大脑进行形态学观察。

结果

行为学研究表明,与对照组相比,暴露于AsO的小鼠某些认知功能(学习和记忆)及运动活动明显下降。同时给予AsO(2、4和8mg/kg体重)和姜黄素(100mg/kg体重)可减轻砷诱导的运动和认知缺陷。单独暴露于AsO也使氧化应激标志物(丙二醛)显著增加,抗氧化酶水平(谷胱甘肽过氧化物酶、谷胱甘肽)下降。高剂量AsO(4和8mg/kg体重)处理的小鼠出现形态学改变。然而,接受AsO+CUR联合处理的小鼠这些变化得到逆转。

结论

总体而言,我们的研究结果表明,姜黄素对纹状体区域具有神经保护作用,可对抗AsO诱导的行为缺陷以及生化和形态学改变。

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