Superoxide anion and other
oxygen-
free radicals have been implicated in the pathogenesis of
bronchopulmonary dysplasia. We tested the hypothesis that a catalytic
antioxidant metalloporphyrin AEOL 10113 can protect against
hyperoxia-induced
lung injury using a fetal baboon model of
bronchopulmonary dysplasia. Fetal baboons were delivered by
hysterotomy at 140 days of gestation (term = 185 days) and given 100%
oxygen for 10 days. Morphometric analysis of alveolar structure showed that fetal baboons on 100%
oxygen alone had increased parenchymal mast cells and eosinophils, increased alveolar tissue volume and septal thickness, and decreased alveolar surface area compared with animals given
oxygen as needed. Treatment with AEOL 10113 (continuous
intravenous infusion) during 100%
oxygen exposure partially reversed these
oxygen-induced changes.
Hyperoxia increased the number of neuroendocrine cells in the peripheral lung, which was preceded by increased levels of urine
bombesin-like
peptide at 48 hours of age. AEOL 10113 inhibited the
hyperoxia-induced increases in urine
bombesin-like
peptide and numbers of neuroendocrine cells. An increasing trend in oxygenation index over time was observed in the 100%
oxygen group but not the mimetic-treated group. These results suggest that AEOL 10113 might reduce the risk of pulmonary
oxygen toxicity in prematurely born infants.