霍诺基通过铁素系统保护重离子辐射诱导的氧化损伤
Yaxiong Chen1, Ruipeng Shen2, Xiedong Zhou2
1State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, and School of Pharmacy, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Space Radiobiology of Gansu Province & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
荣基醇 (HKL) 通过稳定硫素减少酶/硫素 (TrxR/Trx) 系统,防止辐射损伤. 这种天然化合物增强了细胞活力,减少了DNA损伤,并改善了被辐射的小鼠的生存率,显示了辐射保护潜力.
科学领域:
- 辐射生物学 辐射生物学
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 电离辐射暴露对健康构成重大风险,主要是通过基因组不稳定性和氧化应激.
- 红 (HKL),一种天然的双,表现出强大的抗氧化特性.
- 铁素减少酶/铁素 (TrxR/Trx) 反氧化系统在细胞对氧化应激反应中起着至关重要的作用.
研究的目的:
- 调查霍诺基 (HKL) 对电离辐射引起的损伤的辐射保护作用.
- 阐明HKL辐射保护的分子机制,重点关注TrxR/Trx氧化还原系统.
- 在体外细胞模型和体外动物模型中评估HKL的疗效.
主要方法:
- 使用人类支气管上皮细胞 (BEAS-2B) 和C57BL/6小鼠暴露于X射线或碳离子辐射.
- 在细胞实验中使用5.00μM的HKL,在动物实验中使用15.00 mg/kg.
- 采用分子对接和生物化学分析来评估HKL与TrxR/Trx系统的相互作用.
主要成果:
- HKL预处理显著增加了细胞活力,抑制了DNA损伤,并减少了辐射细胞中的活性氧物种 (ROS) 积累.
- 分子对接和测试证实HKL稳定了TrxR/Trx系统,而不会抑制TrxR的催化活性.
- 在小鼠中,HKL减少了辐射诱导的旁观者效应,提高了小鼠的生存率,在肺组织中具有显著的保护作用.
结论:
- 霍诺基 (HKL) 显示出对电离辐射的显著辐射保护潜力.
- 通过调节TrxR/Trx氧化还原系统,HKL提供了辐射保护.
- 这些发现支持HKL作为进一步的临床前评估作为放射性保护剂的有希望的药物.
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