Wang Kai, Li Peng-Fei, Han Chun-Guang, Du Li, Liu Chao, Hu Ming, Lian Shi-Jie, Liu Yong-Xue
a Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China, 100850.
Radiat Res. 2014 Dec;182(6):666-73. doi: 10.1667/RR13823.1.
In previous studies, it has been shown that pretreatment with kojic acid (KA) not only increased the 30 day survival rate of mice after exposed to a lethal dose of gamma radiation but also had significant radioprotective effects on the hematopoietic system, the immune system and DNA of mice exposed to a 4 Gy sublethal dose of radiation. Furthermore, pretreatment with KA has also been shown to protect Chinese hamster ovary (CHO) cells against ionizing radiation-induced damage. In this investigation, beagle dogs were used to evaluate whether KA could also be radioprotective in a large animal model. Dogs in the group pretreated with kojic acid after whole-body exposure to a lethal dose of 3 Gy gamma radiation had a 51 day survival rate of 66.7% versus the dogs in the 3 Gy irradiation only group, which all died within 16 days of postirradiation. General vital signs (body weight or temperature) of animals in the kojic acid pretreated group reduced and increased maximally at day 14 postirradiation and then reverted to normal levels gradually. The hematopoiesis studies indicated that the white blood cells/red blood cells, hemoglobin content and hematocrit of dogs pretreated with kojic acid decreased sharply at day 23/day 21 postirradiation, and then gradually elevated. In addition, the DNA content of dogs pretreated with KA were significantly increased compared with that of dogs in the irradiation group at day 4 postirradiation and the number of micronuclei in the group pretreated with kojic acid declined sharply compared with that of the irradiation only group. KA appears to possess marked protective effects from radiation-induced damage and therefore, may be a promising novel radioprotective agent.
在先前的研究中，已表明用曲酸（KA）预处理不仅能提高小鼠在接受致死剂量γ辐射后的30天存活率，而且对接受4 Gy亚致死剂量辐射的小鼠的造血系统、免疫系统和DNA具有显著的辐射防护作用。此外，用KA预处理还被证明能保护中国仓鼠卵巢（CHO）细胞免受电离辐射诱导的损伤。在本研究中，使用比格犬来评估KA在大型动物模型中是否也具有辐射防护作用。全身暴露于3 Gy致死剂量γ辐射后用曲酸预处理的组中的犬，其51天存活率为66.7%，而仅接受3 Gy辐射的组中的犬在辐射后16天内全部死亡。曲酸预处理组动物的一般生命体征（体重或体温）在辐射后第14天降至最低然后又升至最高，随后逐渐恢复到正常水平。造血研究表明，用曲酸预处理的犬的白细胞/红细胞、血红蛋白含量和血细胞比容在辐射后第23天/第21天急剧下降，然后逐渐升高。此外，与辐射组相比，用KA预处理的犬在辐射后第4天的DNA含量显著增加，并且用曲酸预处理的组中的微核数量与仅辐射组相比急剧下降。KA似乎对辐射诱导的损伤具有显著的保护作用，因此，可能是一种有前景的新型辐射防护剂。
