Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.
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.
Genovese
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Dept of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, Italy.
Cuzzocrea
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S
Di Paola
R
R
Mazzon
E
E
Mastruzzo
C
C
Catalano
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P
Sortino
M
M
Crimi
N
N
Caputi
A P
AP
Thiemermann
C
C
Vancheri
C
C
D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds; D001706:Biopsy; D001761:Bleomycin; D004852:Epoxy Compounds / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007322:Instillation, Drug; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D011897:Random Allocation; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D001761:Bleomycin; D004852:Epoxy Compounds; D019001:Nitric Oxide Synthase; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; D015230:Prostaglandin D2; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014443:Tyrosine; C097240:15-deoxy-delta(12,14)-prostaglandin J2; C002744:3-nitrotyrosine; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds