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Melatonin Modulates Regulation of Nox2 and Nox4 Following Irradiation in the Lung Publisher Pubmed



Najafi M1 ; Shirazi A1 ; Motevaseli E2 ; Geraily G1 ; Amini P3 ; Tooli LF4 ; Shabeeb D5
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Authors Affiliations
  1. 1. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Microbiology, School of Biology, College of Sciences, Tehran University, Tehran, Iran
  5. 5. Department of Physiology, College of Medicine, University of Misan, Misan, Iraq

Source: Current Clinical Pharmacology Published:2019


Abstract

Background: Exposure to ionizing radiation may lead to chronic upregulation of inflammatory mediators and pro-oxidant enzymes, which give rise to continuous production of Reactive Oxygen Species (ROS). NADPH oxidases are among the most important ROS producing enzymes. Their upregulation is associated with DNA damage and genomic instability. In the present study, we sought to determine the expressions of NADPH oxidases; NOX2 and NOX4, in rat’s lung following whole body or pelvis irradiation. In addition, we evaluated the protective effect of melatonin on the expressions of NOX2 and NOX4, as well as oxidative DNA injury. Methods: 35 male rats were divided into 7 groups, G1: control; G2: melatonin (100 mg/kg) treatment; G3: whole body irradiation (2 Gy); G4: melatonin plus whole body irradiation; G5: local irradiation to pelvis area; G6: melatonin treatment plus 2 Gy gamma rays to pelvis area; G7: scatter group. All the rats were sacrificed after 24 h. afterwards, the expressions of TGFβR1, Smad2, NF-κB, NOX2 and NOX4 were detected using real-time PCR. Also, the level of 8-OHdG was detected by ELISA, and NOX2 and NOX4 protein levels were detected by western blot. Results: Whole body irradiation led to the upregulation of all genes, while local pelvis irradiation caused upregulation of TGFβR1, NF-κB, NOX2 and NOX4, as well as protein levels of NOX2 and NOX4. Treatment with melatonin reduced the expressions of these genes and also alleviated oxidative injury in both targeted and non-targeted lung tissues. Results also showed no significant reduction for NOX2 and NOX4 in bystander tissues following melatonin treatment. Conclusion: It is possible that upregulation of NOX2 and NOX4 is involved in radiation-induced targeted and non-targeted lung injury. Melatonin may reduce oxidative stress following upregulation of these enzymes in directly irradiated lung tissues but not for bystander. © 2019 Bentham Science Publishers.
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