Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1? in a Rat Model of Bronchopulmonary Dysplasia

Foetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1? is robustly induced under hypoxia and transactivates many genes that are essential for foetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. In the present study, the authors investigated whether the HIF-1? inducer, deferoxamine (DFX) can improve alveolarisation in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1? and its target genes. Alveolarisation and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1? was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1? in human small airway epithelial cells and to promote the expression of HIF-1? target genes. The authors concluded that the findings from this study suggest that DFX induces and activates HIF-1?, thereby improving alveolarisation and vascular distribution in the lungs of rats with BPD.

Authors: Choi CW, Lee J, Lee HJ, Park HS, Chun YS, Kim BI. ;Full Source: Journal of Korean Medical Science. 2015 Sep;30(9):1295-301. doi: 10.3346/jkms.2015.30.9.1295. Epub 2015 Aug 13. ;