Background Development of lung injury during prolonged O2 exposure is a complex process, associated with changes in expression of a number of genes important in the adaptive response to hyperoxia. MnTBAP is a compound with strong antioxidant properties.
Objective To study the effects of MnTBAP on angiogenic and oxidative gene expression in C57BL6 neonatal mice following hyperoxia.
Design and methods: Newborn mice litters were randomized on postnatal day 4 to hyperoxia (> 95% O2)(OX) or room air (RA) for 72 hrs during which they received MnTBAP (MN) 10mg/kg or saline (SL) daily by IP injection for 3 days and then were sacrificed. Whole lung angiogenic and oxidative gene expression profiling (84 related genes for each) was done by real-time, reverse transcription, quantitative PCR (n=4). Data was processed and analyzed using SA Biosciences PCR array data analysis web portal.
Results Hyperoxia significantly upregulated peroxiredoxin 6 expression compared to room air exposed newborn mice. Treatment with MnTBAP downregulated the expression of myeloperoxidase and Prdx6-rs1. Hyperoxia downregulated the expression of angiogenic genes such as angiopoietin 1 & 2, TGF 1, TGF 3 and HGF; MnTBAP treatment during the hyperoxia exposure reversed this effect and these genes were upregulated.
Conclusions The catalytic antioxidant MnTBAP reversed the effects of hyperoxia on angiogenic gene expression in newborn mice. The protective effects of antioxidants in newborn hyperoxia models need to be studied further to provide additional understanding of the management of bronchopulmonary dysplasia.
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