Effect of rosiglitazone and 15-deoxy-Δ12, 14-prostaglandin J2 on bleomycin-induced lung injury

T. Genovese, Salvator Cuzzocrea, R. Di Paola, E. Mazzon, C. Mastruzzo, P. Catalano, M. Sortino, N. Crimi, A. P. Caputi, C. Thiemermann, C. Vancheri

Research output: Contribution to journalArticle

Abstract

Thiazolidinedione rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-γ ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury. An increase in immunoreactivity to nitrotyrosine, poly(ADP ribose) polymerase (PARP) and inducible nitric oxide synthase as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated mice. Administration of the two PPAR-γ agonists rosiglitazone (10 mg·kg-1 i.p.) and 15d-PGJ2 (30 μg·kg11 i.p.) significantly reduced the: 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity, 4) oedema formation, and 5) histological evidence of lung injury. Administration of rosiglitazone and 15d-PGJ2 also markedly reduced the nitrotyrosine, PARP and inducible nitric oxide synthase formation. In addition, treatment with the PPAR-γ antagonist bisphenol A diglycidyl ether (1 mg·kg-1 i.p. 30 min before the rosiglitazone or 15d-PGJ2) significantly antagonised the effect of the two PPAR-γ agonists. These results demonstrate that the two peroxisome proliferator-activated receptor-γ agonists, rosiglitazone and 15-deoxy-Δ 12,14-prostaglandin J2, significantly reduce lung injury induced by bleomycin in mice.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalEuropean Respiratory Journal
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • 15-deoxy-Δ -prostaglandin J
  • Bleomycin
  • Lung injury
  • Peroxisome proliferator-activated receptor-γ
  • Rosiglitazone

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Effect of rosiglitazone and 15-deoxy-Δ12, 14-prostaglandin J2 on bleomycin-induced lung injury'. Together they form a unique fingerprint.

  • Cite this

    Genovese, T., Cuzzocrea, S., Di Paola, R., Mazzon, E., Mastruzzo, C., Catalano, P., Sortino, M., Crimi, N., Caputi, A. P., Thiemermann, C., & Vancheri, C. (2005). Effect of rosiglitazone and 15-deoxy-Δ12, 14-prostaglandin J2 on bleomycin-induced lung injury. European Respiratory Journal, 25(2), 225-234. https://doi.org/10.1183/09031936.05.00049704