Preclinical evaluation of radiotherapy-induced tongue and esophageal damage in rat head and neck: radioprotective effect of melatonin

ObjectiveThis study aimed to investigate the histopathological and inflammatory alterations induced by single-dose radiotherapy delivered at different dose rates using FF and FFF beams in tongue and esophageal tissues, as well as to assess the potential protective effects of melatonin.Materials and MethodsFourty eight female Sprague–Dawley rats were randomly assigned to six groups (n = 8): control (G1), melatonin (G2), FF-RT (G3), FF-RT + melatonin (G4), FFF-RT (G5), and FFF-RT + melatonin (G6). Radiotherapy was administered as a single 16 Gy dose using a 6 MV photon source. The dose rate was set at 400 MU/min for FF beams and 1400 MU/min for FFF beams. Melatonin was administered intraperitoneally at 10 mg/kg prior to irradiation. All animals were sacrificed 72 h after radiotherapy. Histopathological assessments were performed using H&E, Masson’s trichrome, and toluidine blue staining, while IL-6 expression was analyzed immunohistochemically.ResultsNormal histological structure was preserved in the control (G1) and melatonin-only (G2) groups. Radiation groups (G3 and G5) exhibited significant epithelial disruption, inflammatory cell infiltration, mast cell degranulation, collagen accumulation, and increased IL-6 expression (p < 0.001). In melatonin-treated irradiated groups (G4 and G6), these pathological changes were significantly reduced (p < 0.01). No significant differences were observed between FF and FFF beams (p > 0.05).ConclusionSingle-dose radiotherapy induced comparable inflammatory and fibrotic changes in tongue and esophageal tissues, whereas melatonin administration markedly mitigated these alterations. These findings suggest that melatonin may represent a promising protective agent for reducing radiotherapy-related side effects, with FF and FFF beams exerting similar biological effects on healthy tissues.