en Biomarkers (diagnosis & treatment) Biomarkers (diagnosis & treatment) Original Article Original Article <div style="text-align: justify;">Lung injury is one of the major concerns for chest cancer patients that undergo radiotherapy as well as persons exposed to an accidental radiological event. Reduction/oxidation (redox) system plays a key role in lung injury via chronic upregulation of pro-oxidant enzymes. <em>NOX2</em> and <em>NOX4 </em>are two important reactive oxygen species generating enzymes that are involved in radiation toxicity in some organs such as the bone marrow. In this study, we aimed to evaluate the expression of <em>NOX2</em> and <em>NOX4</em> signaling in rat&rsquo;s lung tissues. Upregulation of these genes may be involved in radiation-induced lung injury. Moreover, we evaluated the role of pre-treatment with melatonin on the expression of these genes. Twenty male rats were divided into 4 groups as control; melatonin treated; irradiation; and irradiation with melatonin pre-treatment. Rats were exposed to 15 Gy ⁶⁰Co gamma rays and sacrificed after 10 weeks for evaluation of <em>NF-&kappa;B</em>, <em>TGF</em><em>bR1</em>, <em>SMAD2</em>, <em>NOX2</em>, and <em>NOX4</em> genes expression by real-time PCR. Results showed the upregulation of all five genes. The expression of <em>NOX2</em> was more obvious compared to other genes. Administration of melatonin before irradiation could attenuate the expression of all mentioned genes. Results indicate that upregulation of NADPH oxidase genes such as <em>NOX2</em> and <em>NOX4</em> may be involved in the late effects of lung exposure to ionizing radiation. Melatonin via downregulation of these pro-oxidant genes is able to attenuate radiation toxicity in the lung.</div> Radiation, Lung, NOX2, NOX4, TGFR1, SMAD2 220 225 http://ijmcmed.org/browse.php?a_code=A-10-1547-2&slc_lang=en&sid=1 Masoud Najafi najafi_ma@yahoo.com 100319475328460014133 100319475328460014133 No Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. alireza shirazi shirazia@sina.tums.ac.ir 100319475328460014134 100319475328460014134 Yes Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Elahe Motevaseli moevaseli-e@tums.ac.ir 100319475328460014135 100319475328460014135 No Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Ghazale Geraily ghazalgh@sina.tums.ac.ir 100319475328460014136 100319475328460014136 No Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Peyman Amini amini.peyman91@yahoo.com 100319475328460014137 100319475328460014137 No Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran. Dheyauldeen Shabeeb shabeeb,dh88@yahoo.com 100319475328460014138 100319475328460014138 No Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences (International Campus), Tehran, Iran. Ahmed Eleojo Musa ahmedmusael@yahoo.com 100319475328460014139 100319475328460014139 No Research center for molecular and cellular imaging, Tehran University of Medical Sciences (International Campus), Tehran, Iran.