Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure

Sheena Bouch, Megan O'Reilly, Richard Harding, Foula Sozo

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18 Citations (Scopus)


Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation, and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21 O2), mild (40 O2), or moderate (65 O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects), or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress (heme oxygenase-1 (HO-1) and nitrotyrosine staining) and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65 O2 group than in the 21 O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40 O2 and 65 O2 groups relative to the 21 O2 group. Exposure to 65 O2, but not 40 O2, led to larger alveoli and lower tissue fraction in the short-term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40 O2 or 65 O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65 O2, 40 O2 does not affect lung architecture.
Original languageEnglish
Pages (from-to)488 - 496
Number of pages9
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5
Publication statusPublished - 2015

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