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Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats.

Morales E, Sakurai R, Husain S, Paek D, Gong M, Ibe B, Li Y, Husain M, Torday JS, Rehan VK - Pediatr. Res. (2014)

Bottom Line: Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation.This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pediatrics, Harbor-University of California Los Angeles (UCLA) Medical Center, Los Angeles Biomedical Research Institute, David Geffen School of Medicine at UCLA, Torrance, California [2] Department of Pediatrics, Children's Hospital Orange County, Orange, California.

ABSTRACT

Background: By stimulating lipofibroblast maturation, parenterally administered peroxisome proliferator-activated receptor γ (PPARγ) agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury.

Methods: One-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24 h; animals were exposed to 21% or 95% O2 for up to 72 h. Twenty-four and 72 h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels.

Results: Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.

Conclusion: Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

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Related in: MedlinePlus

Comparative effects of nebulized RGZ or PGZ on the expression of alveolar epithelial and mesenchymal differentiation markers in the female and male neonatal rat pupThere were no significant differences in the lung protein levels of epithelial, SPB and SPC (A), and mesenchymal, PPARγ, ADRP and leptin, (B), differentiation markers in the female (white bars) and male (black bars) newborn rat pup, 24h following nebulized RGZ or PGZ (n=4; p>0.05, control vs. treated animals).
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Figure 2: Comparative effects of nebulized RGZ or PGZ on the expression of alveolar epithelial and mesenchymal differentiation markers in the female and male neonatal rat pupThere were no significant differences in the lung protein levels of epithelial, SPB and SPC (A), and mesenchymal, PPARγ, ADRP and leptin, (B), differentiation markers in the female (white bars) and male (black bars) newborn rat pup, 24h following nebulized RGZ or PGZ (n=4; p>0.05, control vs. treated animals).

Mentions: At the 24h time-point, there were no major differences in increases in epithelial (Figure 2A) and mesenchymal (Figure 2B) markers of alveolar maturation in males versus females following exposure to nebulized RGZ or PGZ. Similarly, there were no significant differences in male and female responses for the markers of overall alveolar maturation; hence, the combined gender data for [3H] choline incorporation into saturated phosphatidylcholine and [3H] triolein uptake are shown in Figure 1C and 1D.


Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats.

Morales E, Sakurai R, Husain S, Paek D, Gong M, Ibe B, Li Y, Husain M, Torday JS, Rehan VK - Pediatr. Res. (2014)

Comparative effects of nebulized RGZ or PGZ on the expression of alveolar epithelial and mesenchymal differentiation markers in the female and male neonatal rat pupThere were no significant differences in the lung protein levels of epithelial, SPB and SPC (A), and mesenchymal, PPARγ, ADRP and leptin, (B), differentiation markers in the female (white bars) and male (black bars) newborn rat pup, 24h following nebulized RGZ or PGZ (n=4; p>0.05, control vs. treated animals).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4016987&req=5

Figure 2: Comparative effects of nebulized RGZ or PGZ on the expression of alveolar epithelial and mesenchymal differentiation markers in the female and male neonatal rat pupThere were no significant differences in the lung protein levels of epithelial, SPB and SPC (A), and mesenchymal, PPARγ, ADRP and leptin, (B), differentiation markers in the female (white bars) and male (black bars) newborn rat pup, 24h following nebulized RGZ or PGZ (n=4; p>0.05, control vs. treated animals).
Mentions: At the 24h time-point, there were no major differences in increases in epithelial (Figure 2A) and mesenchymal (Figure 2B) markers of alveolar maturation in males versus females following exposure to nebulized RGZ or PGZ. Similarly, there were no significant differences in male and female responses for the markers of overall alveolar maturation; hence, the combined gender data for [3H] choline incorporation into saturated phosphatidylcholine and [3H] triolein uptake are shown in Figure 1C and 1D.

Bottom Line: Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation.This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pediatrics, Harbor-University of California Los Angeles (UCLA) Medical Center, Los Angeles Biomedical Research Institute, David Geffen School of Medicine at UCLA, Torrance, California [2] Department of Pediatrics, Children's Hospital Orange County, Orange, California.

ABSTRACT

Background: By stimulating lipofibroblast maturation, parenterally administered peroxisome proliferator-activated receptor γ (PPARγ) agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury.

Methods: One-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24 h; animals were exposed to 21% or 95% O2 for up to 72 h. Twenty-four and 72 h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels.

Results: Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.

Conclusion: Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

Show MeSH
Related in: MedlinePlus