@article{JTD22913,
author = {Yuanfang Wang and Jiangtao Lin and Jun Shu and Hong Li and Zhencui Ren},
title = {Oxidative damage and DNA damage in lungs of an ovalbumininduced asthmatic murine model},
journal = {Journal of Thoracic Disease},
volume = {10},
number = {8},
year = {2018},
keywords = {},
abstract = {Background: Asthma is characterized to chronic airway inflammation. However, the role of oxidative damage and DNA damage in the pathophysiology of asthma have rarely been studied. On the other hand, there are evidences that DNA-dependent protein kinase (DNA-PK) participates in DNA damage repair and regulates innate immune responses and proinflammatory signaling pathways.
Methods: After ovalbumin (OVA)-induced asthmatic murine model was established, airway hyper-responsiveness (AHR), total and differential bronchoalveolar lavage fluid (BALF) cell counts. IL-4, IL-8, IL-13 and TNF-α were chosen to evaluate the airway inflammation, and oxidative damage indicators levels (8-isoprostane and 8-OhdG) in BALF were measured. Alkaline comet assay was conducted to detected DNA damage. Histological analysis was conducted after hematoxylin and eosin (HE) straining, and proteins were extracted for 3-nitrotyrosine (3-NT) detection and immunoblotting.
Results: AHR, infiltration of inflammatory cells and pro-inflammatory cytokine levels in lungs were significantly higher in asthmatic mice. OVA challenge resulted in robust increase in 3-NT, 8-isoprostane and 8OHdG in lungs, which represented oxidative damage level. DNA damage and repair proteins levels in asthma were also increased. NU7441 aggravated the DNA damage level. However, it suppressed infiltration of lung inflammatory cells and inflammatory cytokine levels, suggesting that DNA-PK may be a potential target for treatment of allergic asthma.
Conclusions: Our study showed that oxidative damage and DNA damage existed in the airway of asthmatic mice. NU7441 augmented DNA damage level, and moreover, it also attenuated infiltration of inflammatory cells and pro-inflammatory cytokine levels in asthmatic lungs.},
issn = {2077-6624}, url = {https://jtd.amegroups.org/article/view/22913}
}