Abstract
This study aimed to evaluate the radioprotective effects of melatonin on healthy thyroid and laryngeal tissues exposed to head and neck radiotherapy using flattening filter (FF) and flattening filter-free (FFF) radiotherapy beams. Forty-eight female Wistar albino rats were randomly assigned to five groups (n = 8): control, only melatonin, FF, FF + melatonin, FFF and FFF + melatonin. A single 16 Gy dose of radiation was delivered to the head and neck region using a linear accelerator. Melatonin (50 mg/kg) was administered intraperitoneally 15 minutes prior to irradiation. Biochemical parameters including malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured from serum samples. Histopathological evaluations of thyroid (inflammation, epithelial hyperplasia, follicular hyperplasia, C-cell hyperplasia, cellular degeneration, follicular cell hypertrophy and cellular necrosis) and laryngeal (general morphological deterioration, inflammation, oedema, epithelial destruction, karyorrhexis and karyolysis) tissues were performed using a semi-quantitative scoring system. FF and FFF beam exposure significantly increased MDA and MPO levels while reducing antioxidant enzyme activities (SOD, CAT, GPx) compared to the control group (P < 0.05). Histologically, both radiation types induced marked inflammation, cellular damage and morphological degeneration in thyroid and laryngeal tissues. Melatonin administration significantly reversed these effects, improving antioxidant enzyme levels and mitigating tissue damage (P < 0.05). No statistically significant difference was observed between FF and FFF groups in either biochemical or histological outcomes. FF and FFF beams produced comparable levels of oxidative and structural damage in healthy tissues. Melatonin demonstrated significant radioprotective effects through both biochemical and histopathological pathways, suggesting its potential role in mitigating radiotherapy-induced toxicity in non-target tissues.