Introduction Randomized trials indicate vitamin A (VA) supplementation decreases bronchopulmonary dysplasia or death in extremely premature infants. It is important to understand the mechanisms by which VA and its derivative retinoic acid (RA) prevent or reverse lung injury.
Aims The hypothesis was that newborn C57BL/6 mice administered VA in combination with RA would reduce hyperoxic lung injury and increase lung retinyl ester (RE) content as compared to animals administered VA, RA, or vehicle alone (canola oil).
Methods Newborn C57BL/6 mice were exposed to 95% O2 or room air from birth and sacrificed at 4 days of age. The agent (VA, RA or the combination VARA)/vehicle was given orally daily. Lungs were evaluated for lung injury (epithelial damage and hemorrhage) by a masked observer, and RE were measured by HPLC in the lung and liver.
Results Hyperoxia led to lung injury, which was reduced more by VARA than by either VA or RA alone (Figure). Epithelial damage and hemorrhage correlated well with each other (r = .94, p < .001). RE levels increased more with VARA than by VA or RA alone (data not shown).
Conclusions Retinoids reduce hyperoxic lung injury in newborn mice. The combination of VA and RA may have synergistic effects on tissue retinoid levels.