Cell death and tissue injury occur as a result of radiation accidents and radiotherapy. The role of endothelial cell damage in mediating radiation-induced acute tissue injury has been extensively studied. We previously demonstrated that ferulic acid (FA) mitigates radiation-induced hematopoietic injury in mice and lessens radiation-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). The purpose of the current study was to determine whether FA can protect HUVECs from radiation toxicity in a cell model via the thrombomodulin (Thbd) pathway, an anti-radiation pathway with anticoagulant, anti-inflammatory and antioxidant properties. HUVEC culture media was supplemented with FA 12 h before 4 Gy 60Co gamma irradiation. At 30 min postirradiation, the FA media was refreshed, then renewed once daily. HUVEC injury was assessed at day 5 postirradiation through cell proliferation analysis. Ferulic acid significantly ameliorated HUVEC radiation injury, as evidenced by increases in cell viability and angiogenesis and decreases in G2/M cell cycle arrest and levels of high mobility group box 1 protein (HMGB1), interleukin (IL)-6 and IL-8. These findings can be attributed to the effect of FA on the Thbd promoter, resulting in increased expression of Thbd and activated protein C with associated radioprotection. These observations indicate that FA intervention significantly ameliorates HUVEC radiation injury via the Thbd pathway. Therefore, FA could be further developed as a potential agent to mitigate radiation-induced damage.
Ferulic Acid Mitigates Radiation Injury in Human Umbilical Vein Endothelial Cells In Vitro via the Thrombomodulin Pathway
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Shuai Shao, Yue Gao, Jianxiang Liu, Mei Tian, Qiao Gou, Xu Su; Ferulic Acid Mitigates Radiation Injury in Human Umbilical Vein Endothelial Cells In Vitro via the Thrombomodulin Pathway. Radiat Res 1 September 2018; 190 (3): 298–308. doi: https://doi.org/10.1667/RR14696.1
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