Extracellular superoxide dismutase protects lung development in hyperoxia-exposed newborn mice.
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.
Ahmed
Mohamed N
MN
Departments of Pediatrics, Medicine, Anesthesiology, Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Suliman
Hagir B
HB
Folz
Rodney J
RJ
Nozik-Grayck
Eva
E
Golson
Maria L
ML
Mason
S Nicholas
SN
Auten
Richard L
RL
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*
D013482:Superoxide Dismutase