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

IF 3.5 3区 医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-10-23 DOI:10.1007/s00213-024-06700-y
Kamlesh Kumar Pandey, Kamakshi Mehta, Balpreet Kaur, Pushpa Dhar
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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 (As2O3) in the mouse striatal region.

Methods: Healthy adult male mice were chronically administered with varying concentrations of As2O3 (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 As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8 mg/kg bw) and curcumin (100 mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 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 As2O3 (4 and 8 mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment.

Conclusions: Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

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姜黄素能减轻三氧化二砷诱发的小鼠纹状体神经损伤。
理由在啮齿类动物中,砷诱发的神经毒性具有剂量依赖性。姜黄素(CUR)是一种具有成本效益的植物多酚,可通过调节氧化应激、细胞凋亡和神经化学作用来保护神经。本研究评估了姜黄素对小鼠纹状体区域三氧化二砷(As2O3)的神经保护潜力。方法:健康成年雄性小鼠单独或与姜黄素(100 毫克/千克体重)一起口服不同浓度的 As2O3(2、4 和 8 毫克/千克体重),连续 45 天。在实验接近尾声时,对动物进行行为范式实验,包括开阔地任务、新物体识别、rota-rod 和 Morris 水迷宫。在第 46 天采集动物纹状体组织进行生化分析(MDA、GPx 和 GSH)。此外,还对灌注固定的大脑进行形态学观察:行为研究表明,与对照组相比,暴露于 As2O3 的小鼠的某些认知功能(学习和记忆)和运动活动明显降低。同时服用 As2O3(2、4 和 8 毫克/千克体重)和姜黄素(100 毫克/千克体重)可减轻砷引起的运动和认知障碍。单独暴露于 As2O3 还会导致氧化应激标记物(MDA)显著增加和抗氧化酶水平(GPx、GSH)下降。摄入高剂量 As2O3(4 毫克/千克体重和 8 毫克/千克体重)的小鼠出现了形态改变。然而,这些变化在接受 As2O3 + CUR 联合治疗的小鼠中得到了逆转:总之,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,可防止 As2O3 引起的行为障碍以及生化和形态学改变。
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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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