Document Type : Original Research


1 PhD, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 MSc, Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran

3 PhD, Department of Physiology, College of Medicine, University of Misan, Misan, Iraq

4 PhD, Research Center of Molecular and Cellular Imaging, Tehran University of Medical Sciences (International Campus), Tehran, Iran

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

6 PhD, Cancer Research Centre, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran


Background: Experimental studies have shown that infiltration of inflammatory cells as well as upregulation of some cytokines play a central role in the development of late effects of ionizing radiation in heart tissues. Evidences have shown that an increased level of TGF-β has a direct correlation with late effects of exposure to ionizing radiation such as chronic oxidative stress and fibrosis. Recent studies have shown that TGF-β, through upregulation of pro-oxidant enzymes such as NOX2 and NOX4, promotes continuous ROS production and accumulation of fibrosis.
Objective: In present study, we aimed to evaluate the expression of NOX2 and NOX4 signaling pathways as well as possible modulatory effects of melatonin on the expression of these genes.
Material and Methods: In this experimental study, four groups of 20 rats (5 in each) were used as follows; G1: control; G2: melatonin; G3: radiation; G4: radiation + melatonin. 100 mg/kg of melatonin was administrated before irradiation of heart tissues with 15 Gy gamma rays. 10 weeks after irradiation, heart tissues were collected for real-time PCR.
Results: Results showed a significant increase in the expression of TGF-β, Smad2, NF-kB, NOX2 and NOX4. The upregulation of NOX2 was more obvious by 20-fold compared to other genes. Except for TGF-β, melatonin could attenuate the expression of other genes.
Conclusion: This study indicated that exposure of rat’s heart tissues to radiation leads to upregulation of TGF-β-NOX4 and TGF-β-NOX2 pathways. Melatonin, through modulation of these genes, may be able to alleviate radiation-induced chronic oxidative stress and subsequent consequences.


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