:: Volume 7, Issue 3 (Int J Mol Cell Med [In press] 2018) ::
Int J Mol Cell Med 2018, 7(3): 0-0 Back to browse issues page
Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Up-regulation of Dual Oxidase Genes Following Rat’s Chest Irradiation
Rasoul Yahyapour 1, Peyman Amini 2, Hana Saffar 3, Saeed Rezapoor 2, Elahe Motevaseli 4, Mohsen Cheki 5, Bagher Farhood 6, Farzad Nouruzi 7, Dheyauldeen Shabeeb 8, Ahmed Eleojo Musa 9, Masoud Najafi * 10
1- School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.
2- Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran.
3- Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
4- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
5- Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
6- Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
7- Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
8- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences (International Campus), Tehran, Iran., Department of Physiology, College of Medicine, University of Misan, Misan, Iraq.
9- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences (International Campus), Tehran, Iran., Research center for molecular and cellular imaging, Tehran University of Medical Sciences (International Campus), Tehran, Iran.
10- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran. , najafi_ma@yahoo.com
Abstract:   (302 Views)
Radiation-induced heart toxicity is one of the serious side effects after  a radiation disaster or radiotherapy for patients with chest cancers, leading to a reduction in the quality of life of the patients. Evidence has shown that infiltration of inflammatory cells plays a key role in the development of functional damages to the heart via chronic up-regulation of some pro-fibrotic and pro-inflammatory cytokines. These changes are associated with continuous free radical production and increased stiffness of heart muscle. IL-4 and IL-13 are two important pro-fibrotic cytokines which contribute to the side effects of exposure to ionizing radiation. Recent studies have proposed that IL-4 through upregulation of DUOX2, and IL-13 via stimulation of DUOX1 gene expression, are involved in the development of late effects of radiation. In the present study, we aimed to detect changes in the expression of these pathways following irradiation of rat’s heart. Furthermore, we evaluated the possible protective effect of metformin on the development of these abnormal changes. 20 male rats were divided into 4 groups (control, radiation, metformin-treated, metformin + radiation). These rats were irradiated with 15 Gy 60Co gamma rays and sacrificed after 10 weeks for evaluation of the changes in the expression of IL4R1IL-13R2aDUOX1, and DUOX2. In addition, the levels of IL-4 and IL-13 cytokines, as well as infiltration of macrophages and lymphocytes were detected. Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of metformin, while the level of IL-13 did not show any significant change. This was associated with infiltration of macrophages and lymphocytes. Also, treatment with metformin could significantly attenuate the accumulation of inflammatory cells, and upregulate these pathways. Therefore, suppression of dual oxidase genes by metformin may be a contributory factor to its protective effect.
Keywords: Radiation, metformin, heart Injury, IL-4, IL-13, DUOX1, DUOX2
Full-Text [PDF 675 kb]   (69 Downloads)    
Type of Study: Original Article | Subject: Biomarkers (diagnosis & treatment)
Received: 2018/08/12 | Accepted: 2018/10/5 | Published: 2018/10/12


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