Radioprotective Activity and Preliminary Mechanisms of N-oxalyl-d-phenylalanine (NOFD) In Vitro

The radiation-induced damage to the human body is primarily caused by excessive reactive oxygen species (ROS) production after irradiation. Therefore, the removal of the increase of ROS caused by ionizing radiation (IR) has been the focus of research on radiation damage protective agents. Hypoxia inducible factor (HIF) is a transcription factor in human and plays an important role in regulating the body metabolism. Factor inhibiting HIF (FIH) is an endogenous inhibitor factor of HIF protein under normoxia conditions. It has been shown that the high expression of HIF protein has a certain repair effect on radiation-induced intestinal injury and hematopoietic system damage in mice; however, it is not clear about the effect of HIF on the level of ROS after radiation. In this study, the role of N-oxalyl-d-phenylalanine (NOFD), an FIH inhibitor, for its effect on alleviating ROS level is investigated in the cells. Our results indicate that pretreatment with NOFD can mitigate ROS level and alleviate IR-induced DNA damage and apoptosis in vitro. Therefore, HIF can be used as a target on scavengers. Furthermore, in order to explore the relevant mechanism, we also test the expression of relevant HIF downstream genes in the cells, finding that Notch-2 gene is more sensitive to NOFD treatment. This experiment result is used to support the subsequent mechanism experiments.