Ferulic Acid Mitigates Radiation Injury in Human Umbilical Vein Endothelial Cells In Vitro via the Thrombomodulin Pathway

Abstract

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 Co 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 G/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.

Tritiated Water Induces Toxicity in Human Umbilical Vein Vascular Endothelial Cells via IL8

“…26 Shao et al also found that ferulic acid can significantly improve the outcomes of HUVECs exposed to radiation by promoting cell viability and angiogenesis and arresting the G2/M cell cycle, which might be associated with decreased levels of HMGB1, IL-6, and IL8. 27 Besides, PRKX expression was also dependent on the amount of exposure, indicating a possible biological dosimeter.…”

Fruits and their phytochemicals in mitigating the ill effects of ionizing radiation: review on the existing scientific evidence and way forward

“…142,143 Feeding black goji berry reduced p53 in intestinal crypt epithelial cells and decreased the caspase-3 and caspase-6 levels in the serum at the 3 rd , 7 th and 14 th -day post-irradiation assay time points 142,143 (Table 1). In addition to the extract, the phytochemicals naringin, [48][49][50][51][52][53] hesperetin, 62 luteolin, 86,87 quercetin, [23][24][25] chlorogenic acid 82,83 and ferulic acid [144][145][146][147][148] possess radioprotective effects (Table 2 and Fig. 1).…”

“…199 Subsequent studies have shown that the whole fruit extract effectively mitigates radiation-induced mucositis and dermatitis in head and neck cancer patients undergoing curative radiotherapy 200 (Table 1). The phytochemicals ferulic acid, [144][145][146][147][148] ellagic acid, 96,97 gallic acid 94,95 and chlorogenic acid 82,83 also possess radioprotective effects.…”

Research progress on the mechanism of radiation enteritis

“…Shao et al. ( 57 ) reported that ferulic acid (FA) can reduce the oxidative damage of radiation to endothelial cells. The thrombomodulin (THBD) pathway may be an important mechanism of FA against radiation injury.…”