The pathogenesis of bronchopulmonary dysplasia is poorly understood. Direct toxic effects of oxygen and endogenous inflammatory responses in the lung are thought to underlie the pulmonary damage. In regard to the latter responses, cytokines including those known to have the potential for producing fibrotic changes in the lung may promote or sustain injury. We have previously demonstrated that dexamethasone (DEX) is effective in prolonging survival of neonatal rats in >98% oxygen if begun between 4 and 6 days of life. We investigated the role of manganese superoxide dismutase (MnSOD) in this protection against hyperoxia. DEX is capable of reducing the expression of many inflammatory cytokines including TNF-α and IL-1-β, cytokines that may play a role in increasing the expression of MnSOD. In hyperoxic animals that received DEX beginning at 4 days of age, MnSOD activity in the lung was 9.8 ± 8.6 U/mg DNA (Mean ± S.D.) without dexamethasone compared to 12 2 ± 10.3 U/mg DNA (Mean ±S.D.) with DEX (p > 0.05). Similarly, mRNA for MnSOD for the former animals was 1.8 × 106 ± 2.0 × 106 copies/μg/RNA (Mean ± S.D.) and for the latter animals 2.8 × 106 ± 2.1 × 106 copies/μg/RNA (Mean ± S.D.) (p > 0.05). For both enzyme activity and mRNA expression for MnSOD there was a trend towards higher levels with DEX treatment although neither reached statistical significance. However, it is questionable that the small increase in activity of MnSOD with DEX could account for the protective effect of DEX in this model. We conclude that mechanisms other than MnSOD are likely operational in protection from hyperoxia in neonatal rats by DEX.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Feb 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)