Curcumin, a potent anti-inflammatory and antioxidant agent, modulates PPARγ signaling, a key molecule in the etiology of Bronchopulmonary Dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for 5 days, as determined at postnatal day (PND) 21. One day old rat pups were exposed to either 21% or 95% O2 for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally once daily, following which the pups grew to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAPK activation following in vitro exposure to hyperoxia for 24h in the presence or absence of curcumin (5μM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis for markers of lung injury [apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes] and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and phosphorylation of Erk 1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation, and that it is a potential intervention against BPD.
- Brochopulmonary Dysplasia
- Copyright © 2013, American Journal of Physiology - Lung Cellular and Molecular Physiology