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Newborn C57BL\/6 mice were exposed to 85% O<jats:sub>2<\/jats:sub>(hyperoxia) or air (normoxia) for 7 or 14 days from birth and given vehicle or VARA every other day. Lung retinol content was measured by HPLC, function was assessed by flexiVent, and development was evaluated by radial alveolar counts, mean linear intercept, and secondary septal crest density. Mediators of oxidative stress, inflammation, and alveolar development were evaluated in lung homogenates. We observed that VARA increased lung retinol stores and attenuated hyperoxia-induced alveolar simplification while increasing lung compliance and lowering resistance. VARA attenuated hyperoxia-induced increases in DNA damage and protein oxidation accompanied with a reduction in nuclear factor (erythroid-derived 2)-like 2 protein but did not alter malondialdehyde adducts, nitrotyrosine, or myeloperoxidase concentrations. Interferon-\u03b3 and macrophage inflammatory protein-2\u03b1 mRNA and protein increased with hyperoxia, and this increase was attenuated by VARA. Our study suggests that the VARA combination may be a potential therapeutic strategy in conditions characterized by VA deficiency and hyperoxia-induced lung injury during lung development, such as bronchopulmonary dysplasia in preterm infants.<\/jats:p>","DOI":"10.1152\/ajplung.00257.2012","type":"journal-article","created":{"date-parts":[[2013,4,13]],"date-time":"2013-04-13T02:33:32Z","timestamp":1365820412000},"page":"L803-L812","source":"Crossref","is-referenced-by-count":49,"title":["VARA attenuates hyperoxia-induced impaired alveolar development and lung function in newborn mice"],"prefix":"10.1152","volume":"304","author":[{"given":"Masheika L.","family":"James","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama;"},{"name":"Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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