Masoud Najafi 1 , Alireza Shirazi 1 , Elahe Motevaseli 2 , Ghazale Geraily 1 , Peyman Amini 3 , Leila Farhadi Tooli 4 , Dheyauldeen Shabeeb 5 Show Affiliations »
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Disease
Gene
Species
Keywords:
Melatonin; NOX2; NOX4; lung; mutation; radiation.
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Year: 2019
PMID： 31057124 DOI： 10.2174/1574884714666190502151733
Source DB: PubMed Journal: Curr Clin Pharmacol ISSN： 1574-8847