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作为抗氧化剂和辐射防护剂的分子氢:来自蒙特卡罗辐射化学模拟的机理见解

Molecular Hydrogen as an Antioxidant and Radioprotector: Mechanistic Insights from Monte Carlo Radiation-Chemical Simulations.

作者信息

Ria Sumaiya Akhter, Meesungnoen Jintana, Jay-Gerin Jean-Paul

机构信息

Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.

出版信息

Antioxidants (Basel). 2025 Aug 27;14(9):1054. doi: 10.3390/antiox14091054.

DOI:10.3390/antiox14091054
PMID:41008961
Abstract

(1) Background: Water, comprising about 70-80% of cellular mass, is the most abundant constituent of living cells. Upon exposure to ionizing radiation, water undergoes radiolysis, generating a variety of reactive species, including free radicals and molecular products. Among these, hydroxyl radicals (OH) are particularly damaging due to their very high reactivity and their capacity to induce oxidative injury to vital biomolecules such as DNA, membrane lipids, and proteins. From a radiation-chemical perspective, this study investigates the selective scavenging ability of molecular hydrogen (H) toward OH radicals, with the aim of evaluating its potential as an antioxidant and radioprotective agent; (2) Methods: We employed our Monte Carlo track chemistry simulation code, IONLYS-IRT, to model the time-dependent yields of ROS in a neutral, aerated aqueous environment. The simulations included varying concentrations of dissolved H and, for comparison, cystamine-a well-known sulfur-containing radioprotector and antioxidant. Irradiation was simulated using 300 MeV protons, chosen to mimic the radiolytic effects of low linear energy transfer (LET) radiation, such as that of Co γ-rays or fast (>1 MeV) electrons; (3) Results: Our simulations quantitatively demonstrated that H selectively scavenges OH radicals. Nevertheless, its scavenging efficiency was consistently lower than that of cystamine, which produced a faster and more pronounced suppression of OH due to its higher reactivity and superior radical-quenching capacity; (4) Conclusions: Molecular hydrogen offers several unique advantages, including low toxicity, high diffusivity, selective scavenging of OH radicals, and well-documented anti-inflammatory effects. Although it is less potent than cystamine in terms of radical-scavenging efficiency, its excellent safety profile and biological compatibility position H as a promising radioprotector and antioxidant for therapeutic applications targeting radiation-induced oxidative stress and inflammation.

摘要

(1)背景:水占细胞质量的70 - 80%,是活细胞中含量最丰富的成分。暴露于电离辐射后,水会发生辐射分解,产生多种反应性物种,包括自由基和分子产物。其中,羟基自由基(OH)因其极高的反应活性以及对DNA、膜脂质和蛋白质等重要生物分子诱导氧化损伤的能力而具有特别的破坏性。从辐射化学角度来看,本研究调查了分子氢(H)对OH自由基的选择性清除能力,旨在评估其作为抗氧化剂和辐射防护剂的潜力;(2)方法:我们使用蒙特卡罗径迹化学模拟代码IONLYS - IRT,对中性、充氧水环境中活性氧(ROS)随时间变化的产率进行建模。模拟包括不同浓度的溶解氢,作为比较,还有胱胺——一种著名的含硫辐射防护剂和抗氧化剂。使用具有300兆电子伏特能量的质子模拟辐照,以模拟低传能线密度(LET)辐射的辐射分解效应,如钴γ射线或快速(>1兆电子伏特)电子的辐射分解效应;(3)结果:我们的模拟定量表明,H能选择性清除OH自由基。然而,其清除效率始终低于胱胺,由于胱胺具有更高的反应活性和更强的自由基猝灭能力,它对OH的抑制作用更快且更显著;(4)结论:分子氢具有几个独特的优势,包括低毒性、高扩散性、对OH自由基的选择性清除以及有充分文献记载的抗炎作用。尽管在自由基清除效率方面它不如胱胺有效,但其出色的安全性和生物相容性使H成为一种有前景的辐射防护剂和抗氧化剂,可用于针对辐射诱导的氧化应激和炎症的治疗应用。

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本文引用的文献

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Oxygen Depletion and the Role of Cellular Antioxidants in FLASH Radiotherapy: Mechanistic Insights from Monte Carlo Radiation-Chemical Modeling.氧耗竭与细胞抗氧化剂在FLASH放疗中的作用:基于蒙特卡罗辐射化学模型的机理洞察
Antioxidants (Basel). 2025 Mar 28;14(4):406. doi: 10.3390/antiox14040406.
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Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application.分子氢疗法:作用机制、给药方法、预防及治疗应用
MedComm (2020). 2025 Apr 28;6(5):e70194. doi: 10.1002/mco2.70194. eCollection 2025 May.
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Functionalized Nanomaterials in Cancer Treatment: A Review.
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Int J Mol Sci. 2025 Mar 14;26(6):2633. doi: 10.3390/ijms26062633.
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A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives.作为缓解氧化应激和疾病的新型营养疗法的分子氢:作用机制与展望的全面综述。
Biochem Biophys Rep. 2025 Jan 25;41:101933. doi: 10.1016/j.bbrep.2025.101933. eCollection 2025 Mar.
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Comparative Analysis of Cystamine and Cysteamine as Radioprotectors and Antioxidants: Insights from Monte Carlo Chemical Modeling under High Linear Energy Transfer Radiation and High Dose Rates.半胱胺与胱胺作为辐射防护剂和抗氧化剂的比较分析:高传能线密度辐射和高剂量率下蒙特卡罗化学建模的见解。
Int J Mol Sci. 2024 Sep 29;25(19):10490. doi: 10.3390/ijms251910490.
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