Radiation-induced cardiotoxicity (RIC) is a significant adverse effect of thoracic radiotherapy (RT), leading to oxidative stress, inflammation, endothelial dysfunction, myocardial fibrosis, vascular damage, and cardiac dysfunction. Melatonin (MLT), a potent antioxidant and radioprotective agent, has been suggested to mitigate these effects. This study aims to evaluate the optimal dosage of MLT for cardioprotection following RT in a rat model. Forty-five adult male Sprague-Dawley rats were divided into five groups. The control group received 1 mL saline solution and sham irradiation. The RT-only group received 12 Gy RT in a single fraction with saline. Three experimental groups received the same RT dose with MLT at 100 mg/kg, 50 mg/kg, or 5 mg/kg. Eight weeks post-irradiation, protein oxidation, lipid peroxidation, glycoxidation, non-enzymatic redox homeostasis biomarkers, and histological changes in heart tissues were examined. In MLT-treated groups, 5 mg/kg dose was found to be more effective in preventing protein oxidation and lipid peroxidation. The levels of advanced glycation end products were significantly lower in 5 mg/kg and 50 mg/kg MLT groups compared to the RT only group, whereas no difference was found at the high dose (100 mg/kg). When Cu-Zn superoxide dismutase activity, iron ion reducing antioxidant power and total thiol groups were evaluated, we found that 5 mg/kg MLT caused a significant increase in these antioxidant parameters, while 50 mg/kg and 100 mg/kg dose caused significant increase in superoxide dismutase. Evaluation heart tissues showed that the RIC was significantly lower in all MLT-treated groups. 5 mg/kg melatonin reduces oxidative markers and RIC in rats, indicating its potential as a low-dose cardioprotective agent after RT.

Purpose: The aim of this study was to test the hypothesis that Tenascin-C (TNC) levels increase following thoracic radiotherapy (RT), and that elevated serum TNC levels are associated with corresponding increases in myocardial TNC expression in histopathological specimens, supporting its role as a potential biomarker of radiation-induced cardiotoxicity. Methods: Blood and cardiac tissue samples from rats 8 weeks after thoracic radiotherapy were analyzed to evaluate changes in serum TNC levels and myocardial TNC expression, and their association with radiation exposure. Male Wistar rats were randomized to a single 12-Gy dose of mediastinal irradiation or sham irradiation. Serum TNC levels were assessed with rat ELISA kits. Myocardial TNC expression was assessed using immunohistochemistry, and staining intensity was semi-quantitatively graded by blinded observers. Results: Serum Tenascin-C (TNC) levels were elevated in RT only group compared to control (p < 0.001), paralleled by a marked increase in myocardial TNC expression (p < 0.001). A consistent concordance between circulating and tissue-level TNC was observed, supporting its potential as a biomarker of radiation-induced cardiac injury. Conclusions: Significant associations were observed between radiation exposure and both serum Tenascin-C levels and myocardial Tenascin-C expression, demonstrating a concordance between circulating and tissue findings and supporting Tenascin-C as a promising biomarker of radiation-induced cardiotoxicity.