Protective effects of swertiamarin against radiation-induced lung injury
10.3760/cma.j.cn112271-20231009-00111-1
- VernacularTitle:獐牙菜苦苷对放射性肺损伤的防护作用
- Author:
Jinyu WANG
1
;
Lixin GONG
;
Zhe ZHAO
;
Gan ZHANG
;
Jingyi LI
Author Information
1. 成都医学院第二附属医院·核工业四一六医院核应激医学中心，成都 610051
- Keywords:
Swertiamarin;
Radiation-induced lung injury;
DNA damage;
Ferroptosis
- From:
Chinese Journal of Radiological Medicine and Protection
2024;44(6):472-481
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the protective effects and mechanism of swertiamarin against ionizing radiation-induced lung injury.Methods:The human bronchial epithelial cells (Beas-2B) and human embryonic lung fibroblasts (HELF) were divided into control group, irradiation group, and irradiation + swertiamarin group, and the effect of swertiamarin on lung cells was detected after X-ray irradiation. Cells exposed to radiation were subjected to detections of lactate dehydrogenase (LDH) release, cell proliferation, and the levels of DNA damage, reactive oxygen species (ROS), lipid peroxides, and iron ions, as well as changes in the contents of ferroptosis-related protein SLC7A11 (xCT) and glutathione peroxidase 4 (GPX4). Moreover, to verify the protective effects of swertiamarin against radiation-induced lung injury in vivo, a mouse model of radiation-induced lung injury was developed. Specifically, C57BL/6J male mice were divided into three groups mentioned above, with five mice in each group. After chest irradiation with 15 Gy X-rays, the lung tissues and serum of the mice were collected at 30 days. The pathological changes in the lung tissues, the level of oxidative stress in these tissues, and changes in the levels of γ-H2AX, GPX4, and inflammatory factors were observed. Results:Compared to the radiation group, the radiation plus swertiamarin group (130 μmol/l) exhibited significant increases in the proliferation rate and clone proliferation rate of cells (Beas-2B: t = 5.50-5.92, P < 0.05; HELF: t = 3.79-5.51, P < 0.05), significant decreases in the LDH release rate, ROS content, lipid peroxide level, and iron ion content of cells (Beas-2B: t=3.00-16.99, P<0.05; HELF: t=4.10-10.97, P<0.05), a significant decrease in the level of DNA damage to cells (Beas-2B: t = 5.69-8.27, P < 0.05; HELF: t = 3.44-14.77, P < 0.05), and increased expression of xCT and GPX4 proteins in cells (Beas-2B: t = 2.90-3.27, P < 0.05; HELF: t = 3.01-7.07, P < 0.05). The in vivo experiments suggested that compared to radiation alone, additional pre-treatment using swertiamarin significantly increased the GSH and GPX4 contents in lung tissues of the mice ( t = 2.31-2.65, P < 0.05), decreased the MDA and γ-H2AX contents in the tissues ( t = 2.71-4.19, P < 0.05), and lowered the levels of IL-6 and IL-1β in the serum of the mice ( t = 3.16-4.56, P < 0.05). Conclusions:Swertiamarin has protective effects against ionizing radiation-induced lung injury by lowering the levels of DNA damage and oxidative stress. The result of this study will provide philosophies for the development of new protective agents against radiation-induced lung injury.
