Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.: PDE4 inhibition and alveolar development

Abstract : BACKGROUND: Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. METHODOLOGY/FINDINGS: Rat pups were placed under hyperoxia (FiO2>95%) or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. CONCLUSIONS: Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2008, 3 (10), pp.e3445. 〈10.1371/journal.pone.0003445〉
Liste complète des métadonnées

Littérature citée [50 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00447993
Contributeur : Georges Guellaen <>
Soumis le : lundi 18 janvier 2010 - 10:17:08
Dernière modification le : jeudi 11 janvier 2018 - 06:20:15
Document(s) archivé(s) le : jeudi 17 juin 2010 - 22:53:30

Fichier

pone.0003445.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Céline Méhats, Marie-Laure Franco-Montoya, Olivier Boucherat, Emmanuel Lopez, Thomas Schmitz, et al.. Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.: PDE4 inhibition and alveolar development. PLoS ONE, Public Library of Science, 2008, 3 (10), pp.e3445. 〈10.1371/journal.pone.0003445〉. 〈inserm-00447993〉

Partager

Métriques

Consultations de la notice

228

Téléchargements de fichiers

155