title: Extracellular superoxide dismutase protects lung development in hyperoxia-exposed newborn mice.
abstract: We tested the hypothesis that targeted transgenic overexpression of human extracellular superoxide dismutase (EC-SOD) would preserve alveolar development in hyperoxia-exposed newborn mice. We exposed newborn transgenic and wild-type mice to 95% oxygen (O2) or air x 7 days and measured bronchoalveolar lavage cell counts, and lung homogenate EC-SOD, oxidized and reduced glutathione, and myeloperoxidase. We found that total EC-SOD activity in transgenic newborn mice was approximately 2.5x the wild-type activity. Hyperoxia-exposed transgenic mice had less pulmonary neutrophil influx and oxidized glutathione than wild-type littermates at 7 days. We measured alveolar surface and volume density in animals exposed to 14 days more of air or 60% O2. Hyperoxia-exposed transgenic EC-SOD mice had significant preservation of alveolar surface and volume density compared with wild-type littermates. After 7 days 95% O2 + 14 days 60% O2, lung inflammation measured as myeloperoxidase activity was reduced to control levels in all treatment groups.
authors.affiliation: Departments of Pediatrics, Medicine, Anesthesiology, Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Ahmed
authors.forename: Hagir B
authors.initials: HB
authors.lastname: Suliman
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Folz
authors.forename: Eva
authors.initials: E
authors.lastname: Nozik-Grayck
authors.forename: Maria L
authors.initials: ML
authors.lastname: Golson
authors.forename: S Nicholas
authors.initials: SN
authors.lastname: Mason
authors.forename: Richard L
authors.initials: RL
authors.lastname: Auten
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D005110:Extracellular Space; D018496:Hyperoxia / Q000201:enzymology*; D008168:Lung / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000502:physiology*
chemical_list: D013482:Superoxide Dismutase