Abstract
BACKGROUND: Radiotherapy applied in the treatment of head and neck cancers significantly increases the risk of developing osteoradionecrosis (ORN). As there is no universally accepted standard treatment protocol for ORN, evaluating the potential therapeutic effects of antioxidant agents such as melatonin and ascorbic acid is of great importance. This study aimed to investigate the effects of these agents on bone healing in an experimental ORN model through histopathological and immunohistochemical analyses. METHODS: A total of 41 young-adult male Wistar-Albino rats were included in the study. All rats in the experimental groups received a single 20 Gy dose of radiotherapy, followed by tooth extraction seven days later. Group G3 received 20 mg/kg of melatonin intraperitoneally for 21 days post-RT and tooth extraction. Group G4 received 100 mg/kg of ascorbic acid intraperitoneally for 21 days. Group G5 received a combination of melatonin and ascorbic acid (20 mg/kg + 100 mg/kg) for the same duration. Immunohistochemical analyses were performed to evaluate bone healing, focusing on the expression of Bone Morphogenetic Protein-2 (BMP-2), Alkaline Phosphatase (ALP), Osteonectin (ONC), and Tartrate-Resistant Acid Phosphatase (TRAP). RESULTS: ALP expression was significantly lower in the G2 group compared to both G1 and G5 (p < 0.05), although the difference was not significant when compared with G3 and G4. BMP-2 expression was significantly reduced in G2 compared to G1 (p < 0.05), but the differences between G2 and G3, G4, G5 were not statistically significant. ONC expression was significantly lower in G2 compared to G1 and G5 (p < 0.05), but not significantly different from G3 and G4. TRAP expression was higher in G2 than all other groups, though this difference did not reach statistical significance. CONCLUSIONS: The findings indicate that melatonin and ascorbic acid may exert protective effects against ORN by enhancing bone healing. TRIAL REGISTRATION: Clinical trial number: not applicable.