Hypoxic stress exacerbates hyperoxia-induced lung injury in a neonatal mouse model of bronchopulmonary dysplasia

Veniamin Ratner, Siarhei Slinko, Irina Utkina-Sosunova, Anatoly Starkov, Richard A. Polin, Vadim S. Ten

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Background: Premature infants with lung injury often experience intermittent episodes of hypoxemia. Objective: This study investigates whether intermittent hypoxemia exacerbates oxidative stress and lung injury in neonatal mice in a hyperoxia-induced model of bronchopulmonary dysplasia (BPD). Methods: For the BPD model, 3-day-old C57Bl/6J mice were exposed to hyperoxia (65% O 2) for 4 weeks (O2 group) or to hyperoxia and intermittent (10 min daily) hypoxia (O2 + H group). Upon completion of O 2 or O2 + H exposure, the degree of pulmonary alveolarization and granulocytic infiltration were examined. The severity of oxidative injury in lungs was defined by tissue glutathione and protein carbonyl content. Data were compared to those in naïve mice and mice subjected only to intermittent hypoxia. Results: Hyperoxia-exposed mice exhibited a dramatic (p < 0.0001) decrease of alveolarization, significantly increased granulocytic infiltration (p < 0.0001) and increased protein carbonyl content (p = 0.04) compared to naïve mice. However, O2 + H mice demonstrated significantly (p = 0.03) fewer alveoli compared to their O 2 counterparts. This was associated with a significantly (p = 0.02) decreased pulmonary total/oxidized glutathione ratio and a significant (p = 0.03) elevation of protein carbonyl content. Conclusions: Thus, intermittent hypoxic stress during hyperoxic induction of BPD in mice potentiates oxidative stress in lung tissue and exacerbates alveolar developmental arrest.

Original languageEnglish
Pages (from-to)299-305
Number of pages7
Issue number4
StatePublished - Jun 2009
Externally publishedYes


  • Bronchopulmonary dysplasia
  • Glutathione
  • Hyperoxia
  • Hypoxia
  • Lung injury
  • Oxidative stress
  • Protein carbonyls


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