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胞磷胆碱和水飞蓟素对γ射线照射大鼠肝损伤和甲状腺激素紊乱的协同作用。

The synergistic effects of citicoline and silymarin on liver injury and thyroid hormone disturbances in γ-irradiated rats.

作者信息

Abdel-Aziz Nahed, El-Bahkery Azza, Ibrahim Ehab A

机构信息

Radiation Biology Research Department, National Center for Radiation Research & Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

出版信息

Mol Biol Rep. 2025 Jan 30;52(1):176. doi: 10.1007/s11033-025-10255-2.

DOI:10.1007/s11033-025-10255-2
PMID:39883250
Abstract

BACKGROUND

Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats.

METHODS AND RESULTS

The rats were exposed to γ-radiation (7 Gy) and treated with citicoline (300 mg/kg/day) and/or silymarin (50 mg/kg/day). The results showed that citicoline alleviated liver damage in irradiated rats by reducing hepatic malondialdehyde levels, serum aspartate aminotransferase activity, and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). It also increased acetylcholine (ACh) levels and the gene expression of the anti-inflammatory protein α7 nicotinic acetylcholine receptor (α7nAChR). Additionally, citicoline improved serum triiodothyronine (T3) levels, thyroid hormone receptor beta (TRβ) gene expression, and iodothyronine deiodinase type 1 activity in hepatic tissues of irradiated rats. Furthermore, citicoline enhanced the effects of silymarin on thyroxine (T4), TRβ, ACh, and α7nAChR when co-administered in irradiated rats. Histopathological analysis confirmed these findings, demonstrating improved liver tissue structure.

CONCLUSIONS

Citicoline mitigates γ-radiation-induced liver damage by reducing oxidative stress, activating the cholinergic anti-inflammatory pathway, and modulating thyroid hormone metabolism. These findings support the use of citicoline as a safe standalone treatment or as an adjuvant with silymarin for managing liver damage and thyroid hormone disturbances caused by γ-irradiation.

摘要

背景

由于电离辐射在工业和医学应用中的广泛使用,接触电离辐射不可避免。寻找有效且安全的天然治疗剂作为化学药物的替代品对于减轻其副作用至关重要。本研究旨在评估胞磷胆碱单独治疗或与抗肝毒性药物水飞蓟素联合使用对保护大鼠免受γ辐射引起的肝损伤的效果。

方法与结果

将大鼠暴露于γ辐射(7 Gy)下,并用胞磷胆碱(300 mg/kg/天)和/或水飞蓟素(50 mg/kg/天)进行治疗。结果表明,胞磷胆碱通过降低肝脏丙二醛水平、血清天冬氨酸转氨酶活性以及肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和核因子-κB(NF-κB)等炎症介质,减轻了受辐照大鼠的肝损伤。它还提高了乙酰胆碱(ACh)水平以及抗炎蛋白α7烟碱型乙酰胆碱受体(α7nAChR)的基因表达。此外,胞磷胆碱改善了受辐照大鼠血清三碘甲状腺原氨酸(T3)水平、甲状腺激素受体β(TRβ)基因表达以及肝组织中1型碘甲状腺原氨酸脱碘酶活性。此外,在受辐照大鼠中联合给药时,胞磷胆碱增强了水飞蓟素对甲状腺素(T4)、TRβ、ACh和α7nAChR的作用。组织病理学分析证实了这些发现,显示肝组织结构得到改善。

结论

胞磷胆碱通过降低氧化应激、激活胆碱能抗炎途径和调节甲状腺激素代谢来减轻γ辐射诱导的肝损伤。这些发现支持将胞磷胆碱作为一种安全的单独治疗方法或作为水飞蓟素的佐剂用于管理γ辐射引起的肝损伤和甲状腺激素紊乱。

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本文引用的文献

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FASEB J. 2024 Sep 15;38(17):e70030. doi: 10.1096/fj.202400823R.
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Radiation-induced fibrosis: Mechanisms and therapeutic strategies from an immune microenvironment perspective.辐射诱导纤维化:从免疫微环境角度看机制和治疗策略。
Immunology. 2024 Aug;172(4):533-546. doi: 10.1111/imm.13788. Epub 2024 Apr 1.
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Silymarin and Inflammation: Food for Thoughts.水飞蓟素与炎症:值得思考的问题。
Antioxidants (Basel). 2024 Jan 14;13(1):98. doi: 10.3390/antiox13010098.
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Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel.水飞蓟素,一种抗氧化黄酮类化合物,可保护肝脏免受抗癌药物紫杉醇的毒性影响。
Tissue Cell. 2023 Aug;83:102158. doi: 10.1016/j.tice.2023.102158. Epub 2023 Jul 7.
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The Role of PY Receptors in the Mechanisms of the Neuroprotective Effect of Citicoline.嘧啶受体在胞磷胆碱神经保护作用机制中的作用。
Bull Exp Biol Med. 2023 May;175(1):45-48. doi: 10.1007/s10517-023-05808-z. Epub 2023 Jun 20.
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