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


CONCLUSIONS
Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.
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.
Edith
E
Morales
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.
Reiko
R
Sakurai
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.
Sumair
S
Husain
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.
Dave
D
Paek
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.
Ming
M
Gong
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.
Basil
B
Ibe
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.
Yishi
Y
Li
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.
Maleha
M
Husain
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.
John S
JS
Torday
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.
Virender K
VK
Rehan
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D018893:Bronchoalveolar Lavage; D002454:Cell Differentiation; D005260:Female; D018496:Hyperoxia / Q000473:pathology; D008168:Lung / Q000254:growth & development*; D055370:Lung Injury / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009330:Nebulizers and Vaporizers; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D000077205:Pioglitazone; D011650:Pulmonary Alveoli / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013501:Surface-Active Agents / Q000737:chemistry; D045162:Thiazolidinediones / Q000008:administration & dosage*
D047495:PPAR gamma; D013501:Surface-Active Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone