Melatonin Modulates Regulation of NOX2 and NOX4 Following Irradiation in the Lung.

IF 3.2 Q2 Pharmacology, Toxicology and Pharmaceutics Current clinical pharmacology Pub Date : 2019-01-01 DOI:10.2174/1574884714666190502151733
Masoud Najafi, Alireza Shirazi, Elahe Motevaseli, Ghazale Geraily, Peyman Amini, Leila Farhadi Tooli, Dheyauldeen Shabeeb
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引用次数: 16

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.

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褪黑素调节肺部照射后NOX2和NOX4的调节。
背景:暴露于电离辐射可能导致炎症介质和促氧化酶的慢性上调,从而导致活性氧(ROS)的持续产生。NADPH氧化酶是产生ROS最重要的酶之一。它们的上调与DNA损伤和基因组不稳定有关。在本研究中,我们试图确定NADPH氧化酶的表达;全身或骨盆照射后大鼠肺中NOX2和NOX4的变化。此外,我们还评估了褪黑素对NOX2和NOX4表达以及DNA氧化损伤的保护作用。方法:35只雄性大鼠分为7组,G1:对照组;G2:褪黑素(100mg /kg)治疗;G3:全身照射(2 Gy);G4:褪黑素加全身照射;G5:骨盆局部照射;G6:褪黑素治疗加2 Gy伽马射线照射骨盆区域;G7:散点组。24 h后处死大鼠,实时荧光定量PCR检测tgf - β r1、Smad2、NF- κB、NOX2、NOX4的表达。ELISA法检测8-OHdG水平,western blot法检测NOX2、NOX4蛋白水平。结果:全身照射导致所有基因上调,骨盆局部照射导致tgf - β r1、NF-κB、NOX2、NOX4以及NOX2、NOX4蛋白水平上调。褪黑素治疗降低了这些基因的表达,也减轻了靶向和非靶向肺组织的氧化损伤。结果还显示,褪黑素治疗后,旁观者组织中的NOX2和NOX4没有显著减少。结论:NOX2和NOX4的上调可能参与了辐射诱导的靶向性和非靶向性肺损伤。褪黑素可能降低氧化应激后,这些酶的上调在直接照射的肺组织,但不是旁观者。
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来源期刊
Current clinical pharmacology
Current clinical pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
3.60
自引率
0.00%
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0
期刊介绍: Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.
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