Nebulized curcumin protects neonatal lungs from antenatal insult in rats.

Intrauterine growth restriction (IUGR) increases the risk of bronchopulmonary dysplasia (BPD), one of the major complications of prematurity. Antenatal low-protein diet (LPD) exposure in rats induces IUGR and mimics BPD-related alveolarization disorders. Peroxisome proliferator-activated receptor-γ (PPARγ) plays a key role in normal lung development and was found deregulated following LPD exposure. The objective of this article was to investigate the effects of nebulized curcumin, a natural PPARγ agonist, to prevent IUGR-related abnormal lung development. We studied rat pups antenatally exposed to an LPD or control diet (CTL) and treated with nebulized curcumin (50 mg/kg) or vehicle from () to . The primary readouts were lung morphometric analyses at . Immunohistochemistry () and microarrays ( and ) were compared within animals exposed to LPD versus controls, with and without curcumin treatment. Quantitative morphometric analyses revealed that LPD induced abnormal alveolarization as evidenced by a significant increase in mean linear intercept (MLI) observed in LPD-exposed animals. Early curcumin treatment prevented this effect, and two-way ANOVA analysis demonstrated significant interaction between diet and curcumin both for MLI [ = 12.67, = 0.001] and radial alveolar count at [ = 6.065, = 0.0182]. Immunohistochemistry for fatty acid binding protein 4 (FABP4), a major regulator of PPARγ pathway, showed a decreased FABP4 alveolar cell density in LPD-exposed animals treated by curcumin. Transcriptomic analysis showed that early curcumin significantly prevented the activation of profibrotic pathways observed at in LPD-exposed animals. Nebulized curcumin appears to be a promising strategy to prevent alveolarization disorders in IUGR rat pups, targeting pathways involved in lung development.