Metabolic support protects oral mucosa from ferroptosis in radiation-induced mucositis

Ionizing radiation is effective in combating cancer but inflicts severe damage on the oral mucosa. The mechanisms behind this damage remain unclear, and current treatment modalities are primarily palliative. This study revealed that ferroptosis is the predominant reason for oral-radiation depletion of oral mucosal epithelial cells. More importantly, compensatory mechanisms are activated in the organism during the early stage after radiation exposure. These compensatory mechanisms arise from the metabolic support provided by fibroblasts. In the early post-radiation stage, fibroblasts supply polyamines, which are readily absorbed by basal epithelial cells, protecting them from ferroptosis. Local supplementation of polyamines effectively mitigates mucosal damage. This study emphasizes the important role of fibroblast-mediated metabolic support in protecting the oral mucosa from radiation-induced damage. Results of the study provide new insights into combating radiation-related diseases by enhancing the self-protective responses of living organisms.