Inhaled vitamin A mitigates hyperoxia-induced acute and chronic lung damage in a neonatal rat model of bronchopulmonary dysplasia.

Authors

Craig A Gelfand, Ying Wang, Reiko Sakurai, Jie Liu, Celia Yu, Gourav Chandan, Sabrina Madrigal, Lisette Juan, Robert Segal, Virender K Rehan

Published in

American journal of respiratory cell and molecular biology. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

Prevention of bronchopulmonary dysplasia (BPD) remains a critical unmet need.
We continued evaluating aerosolized vitamin A in a neonatal rat hyperoxia-injury model of BPD, testing whether lung-targeted inhalation yields superior outcomes compared to enteral or intramuscular (IM) delivery.
Rat pups were exposed to continuous 95% hyperoxia for seven days to induce lung damage. Vitamin A was administered from post-natal day (PD) 1-7 by inhalation, enteral or IM dosing. Persisting effectiveness of inhaled vitamin A was examined at PD 21, dwelling in normoxia after all interventions were discontinued at PD 7.
Comprehensive analyses include alveolar morphometrics, in vivo pulmonary function testing, assessment of hepatic vitamin A level, and quantitating gene and protein expression of relevant biomarkers of lung maturation, inflammation and damage/repair, employing singlex and multiplexed assays and whole-genome gene expression.
Inhaled vitamin A suppressed hyperoxia-induced lung damage, with key hallmarks of BPD, including lung morphometrics and biomarkers associated with lung damage and inflammation, being effectively indistinguishable from healthy controls at both PD 7 and 21, Natural reparative processes were enhanced, with normal alveolarization and pulmonary function at PD 21. Despite raising hepatic vitamin A levels, enteral dosing was ineffective in restoring alveolar morphology at PD 7. Consistent with previous reporting, IM dosing yielded modest effect at PD 7 but with little evidence of benefit to pulmonary function at PD 21. Observation of dose-dependent effects with aerosolized vitamin A strengthens the evidence of the benefits of lung-targeted delivery, supporting further development of inhaled vitamin A as a BPD preventive strategy.

PMID:
42623064
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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