Author/Authors :
Yahyapour, Rasoul School of Medicine- Jiroft University of Medical Sciences, Jiroft , Amini, Peyman Department of Radiology- Faculty of Paramedical- Tehran University of Medical Sciences, Tehran , Saffar, Hana Imam Khomeini Hospital Complex- Tehran University of Medical Sciences, Tehran , Rezapoor, Saeed Department of Radiology- Faculty of Paramedical- Tehran University of Medical Sciences, Tehran , Motevaseli, Elahe Department of Molecular Medicine- School of Advanced Technologies in Medicine- Tehran University of Medical Sciences, Tehran , Cheki, Mohsen Department of Radiologic Technology- Faculty of Paramedicine- Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Farhood, Bagher Departments of Medical Physics and Radiology- Faculty of Paramedical Sciences- Kashan University of Medical Sciences, Kashan , Nouruzi, Farzad Department of Medical Radiation Engineering- Science and Research Branch- Islamic Azad University, Tehran , Shabeeb, Dheyauldeen Department of Physiology- College of Medicine- University of Misan, Misan , Musa, Ahmed Eleojo Department of Medical Physics and Biomedical Engineering- Faculty of Medicine- Tehran University of Medical Sciences (International Campus), Tehran , Najafi, Masoud Radiology and Nuclear Medicine Department- School of Paramedical Sciences- Kermanshah University of Medical Sciences, Kermanshah
Abstract :
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
upregulation 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 ionizing radiation exposure. 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 radiation late effects. 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 IL4R1, IL-13R2a, DUOX1 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 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
