The Radioprotective Effect of Combination of Melatonin and Metformin on Rat Duodenum Damage Induced by Ionizing Radiation: A Histological Study


1 Department of Radiology and Nuclear Medicine, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Science, International Campus, Tehran, Iran; Department of Physiology, College of Medicine, University of Misan, Misan, Iraq

6 Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Science, International Campus; Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran


Background: Radiation toxicity is one of the major concerns for patients with gastrointestinal cancers that undergo radiotherapy. Duodenum is one of the most radiosensitive parts of gastrointestinal system that may be exposed to a high dose of radiation during radiotherapy for some cancers. The development or identification of appropriate radioprotectors with less toxicity is an interesting aim in radiobiology for clinical radiotherapy applications. In the present study, we aimed to evaluate the radioprotective effect of melatonin and metformin combination in rat's duodenum. In addition, we compared our results with the radioprotective effect of melatonin, when administered alone. Materials and Methods: Thirty male rats were divided into six groups: control, melatonin treatment, melatonin plus metformin treatment, whole-body irradiation, irradiation with melatonin treatment, and irradiation with melatonin plus metformin treatment. Irradiation was performed with 10 Gy cobalt-60 gamma rays, while 100 mg/kg of melatonin and metformin were administered 24 h before to 72 h after irradiation. After 3.5 days, their duodenum tissues were removed for histopathological evaluation. Results: Irradiation of rats led to mild-to-moderate mucositis signs, infiltration of inflammatory cells, necrosis, and damage to Brunner's glands and reduction of goblet cells. Melatonin was able to alleviate these damages, while melatonin plus metformin could reduce some radiation toxicity signs.
Conclusion: Administration of melatonin plus metformin could reduce mucositis in duodenum. However, the administration of melatonin is more effective for mitigation of duodenal injury compared with melatonin plus metformin.


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