Title:Melatonin Modulates Regulation of NOX2 and NOX4 Following Irradiation in the Lung
Volume: 14
Issue: 3
Author(s): Masoud Najafi, Alireza Shirazi*, Elahe Motevaseli*, Ghazale Geraily, Peyman Amini, Leila Farhadi Tooli and Dheyauldeen Shabeeb
Affiliation:
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran,Iran
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran,Iran
Keywords:
Melatonin, lung, NOX2, NOX4, radiation, mutation.
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.
