Cardiotoxicity prevention in thoracic radiotherapy: The effect of different melatonin doses on the level of oxidation markers -in vivo animal study.

Introduction: 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. Materials and methods: 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. Results: 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. Conclusion: 5 mg/kg melatonin reduces oxidative markers and RIC in rats, indicating its potential as a low-dose cardioprotective agent after RT.