Zhang Yu-Rui, Li Yuan-Yuan, Wang Jun-Ying, Wang Hua-Wei, Wang Hua-Nan, Kang Xiao-Meng, Xu Wen-Qing
a Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
b Department of Physics, School of Sciences and Tianjin Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300350, China.
Radiat Res. 2017 Sep;188(3):264-275. doi: 10.1667/RR14590.1. Epub 2017 Jun 28.
Mitochondrial dysfunction plays an important role in gamma-radiation-induced mediating oxidative stress. Scavenging radiation-induced reactive oxygen species (ROS) can help mitochondria to maintain their physiological function. Rosmarinic acid is a polyphenol antioxidant that can scavenge radiation-induced ROS, but the structure prevents it from accumulating in mitochondria. In this study, we designed and synthesized a novel rosmarinic acid derivative (Mito-RA) that could use the mitochondrial membrane potential to enter the organelle and scavenge ROS. The DCFH-DA assay revealed that Mito-RA was more effective than rosmarinic acid at scavenging ROS. DNA double-strand breaks, chromosomal aberration, micronucleus and comet assays demonstrated the ability of Mito-RA to protect against radiation-induced oxidative stress in vitro. These findings demonstrate the potential of Mito-RA as an antioxidant, which can penetrate mitochondria, scavenge ROS and protect cells against radiation-induced oxidative damage.
线粒体功能障碍在γ辐射诱导的氧化应激介导中起重要作用。清除辐射诱导的活性氧（ROS）有助于线粒体维持其生理功能。迷迭香酸是一种多酚抗氧化剂，可清除辐射诱导的ROS，但其结构阻止其在线粒体中积累。在本研究中，我们设计并合成了一种新型迷迭香酸衍生物（Mito-RA），它可以利用线粒体膜电位进入细胞器并清除ROS。DCFH-DA检测表明，Mito-RA在清除ROS方面比迷迭香酸更有效。DNA双链断裂、染色体畸变、微核和彗星试验证明了Mito-RA在体外预防辐射诱导的氧化应激的能力。这些发现证明了Mito-RA作为一种抗氧化剂的潜力，它可以穿透线粒体，清除ROS并保护细胞免受辐射诱导的氧化损伤。
