Peroxisome Proliferator-Activated Receptor ? Agonists Enhance Lung Maturation in a Neonatal Rat Model

The nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) ? plays a central role in normal lung development. However, the effects of modulating PPAR? expression by exogenously administered PPAR? agonists on lung development and basic blood biochemical and metabolic profiles in a developing animal are not known. To determine these effects, newborn Sprague-Dawley rat pups were administered either diluent or rosiglitazone (RGZ), a potent PPAR? agonist, for either 1 or 7 d. Then the pups were killed and the lungs were examined for specific markers of alveolar epithelial, mesenchymal, and vascular maturation, and lung morphometry. The effect of RGZ on a limited number of blood biochemical and metabolic parameters was also determined. Overall, systemically administered RGZ significantly enhanced lung maturation without affecting serum electrolytes, blood glucose, blood gases, plasma cholesterol, triglycerides, and serum cardiac troponin levels. The lung maturation effect of PPAR? agonists was also confirmed by another PPAR? agonist, the naturally occurring PPAR? ligand prostaglandin J2. We conclude that systemically administered RGZ significantly enhances lung maturation without significantly affecting the acute blood biochemical and metabolic profiles, providing rationale for further studying PPAR? agonists for enhancing lung maturation, and for promoting lung injury/repair in neonates.