Effect of rosiglitazone and 15-deoxy- 12,14-prostaglandin J2 on bleomycin-induced lung injury

Autor: Genovese, Tiziana, Cuzzocrea, Salvatore, DI PAOLA, R, Mazzon, E, Mastruzzo, C, Catalano, P, Sortino, M, Crimi, N, Caputi, Achille, Thiemermann, C, Vancheri, C., DI PAOLA, Rosanna
Rok vydání: 2005
Předmět:
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
medicine.drug_class
Biopsy
Pulmonary Fibrosis
Peroxisome proliferator-activated receptor
Prostaglandin
Lung injury
Bleomycin
bleomycin
15-deoxy-Delta(12
14)-prostaglandin J(2)
lung injury
peroxisome proliferator-activated receptor-gamma
rosiglitazone
Immunoenzyme Techniques
Rosiglitazone
Mice
Random Allocation
chemistry.chemical_compound
Internal medicine
Weight Loss
Animals
Medicine
Benzhydryl Compounds
Thiazolidinedione
Peroxidase
chemistry.chemical_classification
Analysis of Variance
biology
Prostaglandin D2
business.industry
Nitrotyrosine
Nitric oxide synthase
Instillation
Drug
Endocrinology
chemistry
biology.protein
Epoxy Compounds
Tyrosine
Thiazolidinediones
lipids (amino acids
peptides
and proteins)
Nitric Oxide Synthase
Poly(ADP-ribose) Polymerases
business
medicine.drug
Zdroj: European Respiratory Journal. 25:225-234
ISSN: 1399-3003
0903-1936
DOI: 10.1183/09031936.05.00049704
Popis: Thiazolidinedione rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-gamma 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-gamma agonists rosiglitazone (10 mg x kg(-1) i.p.) and 15d-PGJ2 (30 microg x kg(-1) 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-gamma antagonist bisphenol A diglycidyl ether (1 mg x kg(-1) i.p. 30 min before the rosiglitazone or 15d-PGJ2) significantly antagonised the effect of the two PPAR-gamma agonists. These results demonstrate that the two peroxisome proliferator-activated receptor-gamma agonists, rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, significantly reduce lung injury induced by bleomycin in mice.
Databáze: OpenAIRE
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