Hypoxic stress exacerbates hyperoxia-induced lung injury in a neonatal mouse model of bronchopulmonary dysplasia.
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 (O(2) group) or to hyperoxia and intermittent (10 min daily) hypoxia (O(2) + H group). Upon completion of O(2) or O(2) + 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, O(2) + 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.
Ratner
Veniamin
V
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. vr158@columbia.edu
Slinko
Siarhei
S
Utkina-Sosunova
Irina
I
Starkov
Anatoly
A
Polin
Richard A
RA
Ten
Vadim S
VS
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000150:complications* / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D050050:Protein Carbonylation / Q000502:physiology; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D005978:Glutathione; D010100:Oxygen