Does lack ofglutathione peroxidase 1gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?

Abstract

Supplemental oxygen (O) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing () gene expression increases the injurious effects of hyperoxia (Hyp). and C57Bl/6J mice were exposed to 21% O (Air) or 40% O (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and and gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of expression and further decreased by hyperoxia. expression was increased in Hyp mice and decreased in both groups. On P56d, heme oxygenase-1 was increased by hyperoxia when was absent. There were significantly more immune cells from Hyp groups than from theAir group and a greater proportion of lymphocytes in Hyp mice. expression was significantly decreased in mice; and expression was increased inHyp mice compared with other groups. Tissue fraction was decreased in Air mice; bronchiolar smooth muscle was decreased in mice. does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of and inHyp mice suggests gene redundancy within the model.

Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation

“…Surprisingly low is also the number of mouse experimental studies assessing long-term oxidative damages of lung proteins [18, 19], and no study determined the current rate of lung ROS formation in adulthood. As we supposed similarities in the persistent lung changes due to neonatal hyperoxia between human and mouse, our study aimed at the identification of emphysema-like lung phenotype and its possible relation to oxidative stress-related parameters in adult mice exposed as newborns to moderate vs. severe hyperoxic air conditions (50 vs. 75% O 2 ).…”

Mouse genetic background impacts susceptibility to hyperoxia‐driven perturbations to lung maturation

“…This is potentially important because disturbances to glutathione dynamics have been noted in hyperoxia‐exposed newborn rat lungs, although the role of the glutathione metabolizing machinery in aberrantly developing immature lungs remains unclear. To date, genetic ablation of Gpx1 , one of six GPX enzymes, was without impact on lung alveolarization in the hyperoxia‐based animal model of BPD, possibly due to compensation by other isozymes. Similarly, overexpression of glutathione reductase in alveolar type II cells in adult mice did not protect against hyperoxic lung injury, although that study did not address lung alveolarization in neonates.…”

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

“…The long-term effect of hyperoxia on the expression of HIF-1 α and catalase in the proximal tubules was also investigated in the current study, which demonstrated that HIF-1 α and catalase expression in mature proximal tubules was downregulated following neonatal hyperoxia. However, neonatal mice exposed to hyperoxia for the first 7 days of life did not show altered catalase mRNA expression in mature lung tissue [64]. Differences in the tissues studied and the duration of exposure to hyperoxia may have resulted in the discrepancy between two studies.…”