Background: Oxygen therapy and mechanical ventilation are important predisposing factors for the development of bronchopulmonary dysplasia (BPD), leading to increased morbidity and mortality in premature infants. Oxygen toxicity mediated by reactive oxygen species (ROS) may play an important part in the development of BPD. We studied the effects of MnTBAP, a catalytic antioxidant on airway responsiveness and alveolar simplification in adult mice following neonatal hyperoxia.
Methods: Mice litters were randomized to 85 %O2 or room air (RA) on D3 for 12 days to receive either MnTBAP (10 mg/kg/d) or saline intraperitoneally. Methacholine challenge (MCC) performed at 8 and 12 weeks of age by whole-body plethysmography to assess airway reactivity. Alveolarization quantified on lung sections by radial alveolar count (RAC) and mean linear intercept (MLI). Cell counts assessed from bronchoalveolar lavage (BAL) performed at 15 weeks.
Results: Mice exposed to hyperoxia and MnTBAP (OXMN) had significantly higher airway reactivity post-MCC at 8 weeks compared to RA and O2 groups. At 12 weeks, airway reactivity was higher post-MCC in both hyperoxia and OXMN groups. MnTBAP did not attenuate hyperoxia-induced airway reactivity in adult mice. Hyperoxia exposed mice demonstrated large and distended alveoli on histopathology at 2 and 15 weeks. MnTBAP did not ameliorate hyperoxia-induced lung injury as assessed by RAC/MLI. Absolute lymphocyte count was significantly higher in BAL in the hyperoxia and OXMN groups.
Conclusions: MnTBAP, a catalytic antioxidant, did not afford protection from hyperoxia-induced lung injury in adult mice.
Keywords: Hyperoxia; Lung injury; Methacholine; MnTBAP; Newborn mice.
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.