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胞磷胆碱对大鼠头部照射后诱导的脑线粒体功能障碍的影响。

The impact of citicoline on brain mitochondrial dysfunction induced in rats after head irradiation.

作者信息

Abdel-Aziz Nahed, Algeda Fatma Rabia, Shedid Shereen M

机构信息

Radiation Biology Research Department, National Center for Radiation Research & Technology, Egyptian Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt.

出版信息

Sci Rep. 2025 Jul 15;15(1):25658. doi: 10.1038/s41598-025-11098-4.

DOI:10.1038/s41598-025-11098-4
PMID:40665089
Abstract

Head irradiation is a common treatment for brain cancer; however, it can cause side effects in healthy brain tissue. This study aimed to test whether citicoline administration modulates radiation-induced brain mitochondrial dysfunction in rats. The head of the animal was exposed to 10 Gy γ-radiation. Citicoline (300 mg/kg body weight/day) was administered intraperitoneally for four weeks after irradiation. Some biochemical changes related to mitochondrial function in brain tissue were studied. The results showed that citicoline administration after head irradiation reduced oxidative stress, enhanced the activity of mitochondrial complexes (I and II), increased the aconitase enzyme activity, boosted ATP production, and restored the levels of calcium, iron, and caspase-3, compared to the corresponding values in irradiated rats. The levels of glucose and cholesterol in brain tissue were modulated. Citicoline also increased acetylcholine level and alpha-7 nicotinic receptor mRNA expression and decreased acetylcholinesterase activity in the brain tissue of irradiated-treated rats. We concluded that citicoline could attenuate the harmful effects of γ-radiation on the brain by modulating mitochondrial function, neurotransmission, and calcium & iron homeostasis, thus suppressing the mitochondrial-mediated apoptosis pathway. However, additional studies are required to validate and confirm these results before any clinical application can be recommended.

摘要

头部照射是脑癌的常见治疗方法;然而,它会对健康脑组织产生副作用。本研究旨在测试给予胞磷胆碱是否能调节大鼠辐射诱导的脑线粒体功能障碍。将动物头部暴露于10 Gy的γ辐射下。照射后腹腔注射胞磷胆碱(300 mg/kg体重/天),持续四周。研究了与脑组织线粒体功能相关的一些生化变化。结果表明,与照射大鼠的相应值相比,头部照射后给予胞磷胆碱可降低氧化应激,增强线粒体复合物(I和II)的活性,增加乌头酸酶活性,提高ATP生成,并恢复钙、铁和半胱天冬酶-3的水平。脑组织中的葡萄糖和胆固醇水平得到调节。胞磷胆碱还增加了照射处理大鼠脑组织中的乙酰胆碱水平和α-7烟碱受体mRNA表达,并降低了乙酰胆碱酯酶活性。我们得出结论,胞磷胆碱可通过调节线粒体功能、神经传递以及钙和铁稳态来减轻γ辐射对大脑的有害影响,从而抑制线粒体介导的凋亡途径。然而,在推荐任何临床应用之前,还需要进一步的研究来验证和确认这些结果。

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本文引用的文献

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Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature.基于线粒体的神经退行性疾病治疗方法:当前文献综述
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Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders.
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SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.SCARLET(补充胞磷胆碱治疗降低肺损伤疗效试验):一项单中心、双盲、安慰剂对照、随机 1/2 期临床试验的研究方案,旨在评估静脉注射胞磷胆碱(胞二磷胆碱)治疗 SARS-CoV-2 感染合并低氧性急性呼吸衰竭住院患者的疗效。
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