Hyperoxia is a major cause of lung injury in premature infants and along with other risk factors contributes to the development of bronchopulmonary dysplasia (BPD). To assess if azithromycin, a macrolide antibiotic with anti-inflammatory effects, could be beneficial for the treatment of BPD we conducted an experiment to evaluate the effects of azithromycin in neonatal rats exposed to hyperoxia. A total of 64 rats were divided equally into 4 groups: room air control, room air azithromycin, hyperoxia control, and hyperoxia azithromycin. The hyperoxia groups were exposed to > 95% oxygen from day of life 4 to day 14. Animals who completed the experiment (n = 56) were sacrificed for histologic analysis of their lungs and protein analysis of lung tissue lysate. Mean linear intercept (MLI) was significantly lower in the control groups vs the hyperoxia groups (p < .001). The hyperoxia azithromycin group had a lower MLI compared to the hyperoxia control group (61 vs 75.5, respectively) (p = .03). IL-6 values of lung homogenate were lower in the hyperoxia azithromycin group vs the hyperoxia control group (p = .04). The NF-kB p65 values of lung homogenate, which were evaluated using Western blot analysis, were increased in the hyperoxia azithromycin compared to the hyperoxia control group. Our experiment suggests that azithromycin is protective against the effects of hyperoxia as demonstrated by improved lung histology and decreased IL-6 levels. The mechanism for the elevated NF-kB p65 levels remains unknown but appears to be associated with lung protection from the toxic effects of hyperoxia.
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