Author/Authors :
Aliasgharzadeh ، Akbar - Kashan University of Medical Sciences , Farhood ، Bagher - Kashan University of Medical Sciences , Amini ، Peyman - Tehran University of Medical Sciences , Saffar ، Hana - Clinical and Anatomical Pathologist at Tehran University of Medical Science , Motevaseli ، Elahe - Tehran University of Medical Sciences , Rezapoor ، Saeed - Tehran University of Medical Sciences , Nouruzi ، Farzad - Islamic Azad University , Shabeeb ، Dheyauldeen - Tehran University of Medical Sciences (International Campus) , Eleojo Musa ، Ahmed - Tehran University of Medical Sciences (International Campus) , Mohseni ، Mehran - Kashan University of Medical Sciences , Moradi ، Habiballah - Kashan University of Medical Sciences , Najafi ، Masoud - Kermanshah University of Medical Sciences
Abstract :
Objective The Lung is one of the most radiosensitive organs of the body. The infiltration of macrophages and lymphocytes into the lung is mediated via the stimulation of Thelper 2 cytokines such as IL4 and IL13, which play a key role in the development of fibrosis. It is likely that these cytokines induce chronic oxidative damage and inflammation through the upregulation of Duox1, and Duox2, which can increase the risk of late effects of ionizing radiation (IR) such as fibrosis and carcinogenesis. In the present study, we aimed to evaluate the possible increase of IL4 and IL13 levels, as well as their downstream genes such as IL4ra1, IL13ra2, Duox1, and Duox2. Materials and Methods In this experimental animal study, male rats were divided into 4 groups: i. Control, ii. Melatonin treated, iii. Radiation, and iv. Melatonin (100 mg/kg) plus radiation. Rats were irradiated with 15 Gy 60Co gamma rays and then sacrificed after 67 days. The expressions of IL4ra1, IL13ra2, Duox1, and Duox2, as well as the levels of IL4 and IL13, were evaluated. The histopathological changes such as the infiltration of inflammatory cells, edema, and fibrosis were also examined. Moreover, the protective effect of melatonin on these parameters was also determined. Results Results showed a 1.5fold increase in the level of IL4, a 5fold increase in the expression of IL4ra1, and a 3fold increase in the expressions of Duox1, and Duox2. However, results showed no change for IL13 and no detectable expression of IL13ra2. This was associated with increased infiltration of macrophages, lymphocytes, and mast cells. Melatonin treatment before irradiation completely reversed these changes. ConclusionThis study has shown the upregulation of IL4IL4ra1Duox2 signaling pathway following lung irradiation. It is possible that melatonin protects against IRinduced lung injury via the downregulation of this pathway and attenuation of inflammatory cells infiltration.
Keywords :
Duox1 , Duox2 , Lung , Melatonin , Radiation ,
