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

Aliasgharzadeh, A. and Farhood, B. and Amini, P. and Saffar, H. and Motevaseli, E. and Rezapoor, S. and Nouruzi, F. and Shabeeb, D. and Musa, A.E. and Mohseni, M. and Moradi, H. and Najafi, M. (2019) Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats. Cell Journal, 21 (3). pp. 236-242.

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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. 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 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. © 2019 Royan Institute (ACECR). All rights reserved.

Item Type: Article
Additional Information: cited By 3
Uncontrolled Keywords: duox1 enzyme; duox2 enzyme; interleukin 13; interleukin 13 receptor alpha2; interleukin 4; interleukin 4 receptor alpha; melatonin; oxygenase; unclassified drug, animal cell; animal model; animal tissue; Article; cell infiltration; controlled study; cytokine release; edema; fibrosis; gamma radiation; histopathology; inflammatory cell; lung injury; lymphocyte; macrophage; male; mast cell; neutrophil chemotaxis; nonhuman; radiation dose; radiation injury; rat; receptor upregulation; signal transduction; thorax radiography
Subjects: Physiology
Divisions: Faculty of Medicine > Basic Sciences > Department of physiology
Depositing User: ART . editor
Date Deposited: 01 Jan 2020 15:17
Last Modified: 01 Jan 2020 15:17

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