Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells
Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells
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DOI：
10.1096/fj.201802246rr
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发表时间：
2019-06-01
期刊：
影响因子：
4.8
通讯作者：
Kunugita, Naoki
中科院分区：
文献类型：
--
作者：
Shimura, Tsutomu;Koyama, Mao;Kunugita, Naoki
由于核事故或使用放射性材料的恐怖主义而导致的意外辐射暴露对人类健康具有严重的不利影响，根据辐射的剂量和分布，可能会表现为急性辐射综合症。因此，迫切需要开发辐射对抗剂来保护人类免受辐射伤害。除了核 DNA 之外，线粒体也是电离辐射 (IR) 的重要目标，因为这些细胞器会产生活性氧 (ROS)。最近，我们发现线粒体 ROS 激活的细胞信号传导与 IR 诱导的肿瘤形成有关。在这里，我们利用人体细胞和小鼠研究了抗坏血酸和表儿茶素 (EC) 作为辐射对抗剂清除 ROS 的有效性。 EC 辐射前和辐射后治疗可减轻 ROS 介导的线粒体损伤、IR 诱导的氧化应激反应，包括超氧化物歧化酶活性降低和核因子红细胞 2 相关因子 2 表达升高，并改善人成纤维细胞存活率。在体外，EC 减轻了小鼠血小板体内暴露于 IR 后 ROS 介导的线粒体损伤。此外，口服EC显着增强了小鼠体内辐射损伤造血细胞的恢复。总之，EC 是一种潜在可行的对策剂，通过靶向线粒体介导的氧化应激，可立即有效地对抗意外的红外线照射。-Shimura, T.、Koyama, M.、Aono, D.、Kunugita, N。表儿茶素是一种有前景的药剂，可通过减轻人类成纤维细胞和小鼠造血细胞的线粒体损伤来对抗辐射照射。
Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS-activated cell signaling is associated with IR-induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS-mediated mitochondrial damage, IR-induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2-related factor 2 expression, and they improve human fibroblast survival. As well as in vitro, EC mitigated ROS-mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo. In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria-mediated oxidative stress.-Shimura, T., Koyama, M., Aono, D., Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells.