Protective effects of swertiamarin against radiation-induced lung injury
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 y-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.
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