Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats

Akbar Aliasgharzadeh; Bagher Farhood; Peyman Amini; Hana Saffar; Elahe Motevaseli; Saeed Rezapoor; Farzad Nouruzi; D Heyauldeen Shabeeb; Ahmed Eleojo Musa; Mehran Mohseni; Habiballah Moradi; Masoud Najafi

doi:10.22074/cellj.2019.6207

Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats

Cell J. 2019 Oct;21(3):236-242. doi: 10.22074/cellj.2019.6207. Epub 2019 Jun 15.

Authors

Affiliations

¹ Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
² Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran.
³ Clinical and Anatomical Pathologist at Tehran University of Medical Science, Imam Khomeini Hospital Complex, Tehran, Iran.
⁴ Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
⁶ Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences (International Campus), Tehran, Iran.
⁷ Department of Physiology, College of Medicine, University of Misan, Misan, Iraq.
⁸ Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences (International Campus), Tehran, Iran.
⁹ Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic Address: najafi_ma@yahoo.comg.

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 T-helper 2 cytokines such as IL-4 and IL-13, 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 IL-4 and IL-13 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. Melatonintreated, 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 IL-4 and IL-13, 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 1.5-fold increase in the level of IL-4, a 5-fold increase in the expression of IL4ra1, and a 3-fold increase in the expressions of Duox1 and Duox2. However, results showed no change for IL-13 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.

Conclusion: This study has shown the upregulation of IL-4-IL4ra1-Duox2 signaling pathway following lung irradiation. It is possible that melatonin protects against IR-induced lung injury via the downregulation of this pathway and attenuation of inflammatory cells infiltration.

Keywords: Duox1; Duox2; Lung; Melatonin; Radiation.