Aerosolized deferoxamine administration in mouse model of bronchopulmonary dysplasia improve pulmonary development

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm newborns. It occurs due to early exposure to high-oxygen and ventilation therapy. The mechanisms of disrupted alveolarization and vascular development associated with BPD were unclear. Deferoxamine (DFO) has been reported to reduce mortality and lung injury in mice after chlorine exposure. The effect of DFO in the treatment of BPD has not been explored. This study aimed to investigate the effect of aerosolized DFO administration in a mouse model of BPD. A mouse model of oxygen-induced BPD was established by postnatal hyperoxia (75% oxygen for 7 days) and DFO [17 mg/(kg·day)] (BPD+D) or aerosolized vehicle (BPD+V) administered for 14 days. The mice were anesthetized and sacrificed after 14 days treatment before removing the lungs for analysis. An exogenous continuous aerosol of DFO exerted a biological effect on BPD mice. The BPD+DFO group showed a better weight gain compared with the BPD+V group. Furthermore, the treatment of DFO exhibited a reduced pathological severity and increase expression of hypoxia-inducible factor (HIF)-1α and CD31, and activated downstream vascular endothelial growth factor (VEGF)-induced angiogenesis. The results showed that C57BL/6 mice exposed to hyperoxic environment and treated with aerosolized of DFO solution, obviously promoted the pulmonary vascularization and alveolarization. The HIF-1α/VEGF signaling pathway mediated this process. The findings indicated that treatment with an exogenous continuous aerosol of DFO might be a potential therapeutic strategy for BPD.