16,16-Dimethyl prostaglandin E2 efficacy on prevention and protection from bleomycin-induced lung injury and fibrosis.
In this study, we evaluated the protective effect and therapeutic potential of the prostaglandin E(2) (PGE(2)) synthetic analog 16,16-dimethyl-PGE(2) (dmPGE(2)) in the animal model of pulmonary fibrosis induced by bleomycin. Mice subjected to intratracheal administration of bleomycin (1 mg/kg) received a dmPGE(2) dose of 30 microg/kg/day by continuous subcutaneous infusion. Bronchoalveolar lavage (BAL); immunohistochemical analysis for IL-1, TNF-alpha, and nitrotyrosine; measurement of fluid content in lung; myeloperoxidase activity assay; and lung histology were performed 1 week later. Lung histology and Sircol assay for collagen deposition were performed 3 weeks after treatments. Changes of body weight and survival rate were also evaluated at 1 and 3 weeks. Compared with bleomycin-treated mice, dmPGE(2) co-treated mice exhibited a reduced degree of body weight loss and mortality rate as well as of lung damage and inflammation, as shown by the significant reduction of: (1) lung infiltration by leukocytes; (2) myeloperoxidase activity; (3) IL-1, TNF-alpha, and nitrotyrosine immunostaining; (4) lung edema; and (5) histologic evidence of lung injury and collagen deposition. In a separate set of experiments, dmPGE(2) treatment was started 3 days after bleomycin administration, and the evaluation of lung damage and inflammation was assessed 4 days later. Importantly, delayed administration of dmPGE(2) also was able to protect from inflammation and lung injury induced by bleomycin. These results, indicating that dmPGE(2) is able to prevent and to reduce bleomycin-induced lung injury through its regulatory and anti-inflammatory properties, encourage further research to find new options for the treatment of pulmonary fibrosis.
Failla
Marco
M
Department of Internal Medicine and Specialistic Medicine, Respiratory Diseases Section, University of Catania, Via Passo Gravina, Catania, Italy.
Genovese
Tiziana
T
Mazzon
Emanuela
E
Fruciano
Mary
M
Fagone
Evelina
E
Gili
Elisa
E
Barera
Annalisa
A
La Rosa
Cristina
C
Conte
Enrico
E
Crimi
Nunzio
N
Cuzzocrea
Salvatore
S
Vancheri
Carlo
C
D015064:16,16-Dimethylprostaglandin E2 / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001761:Bleomycin; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D055104:Infusions, Subcutaneous; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D053583:Interleukin-1beta; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D009195:Peroxidase; D015064:16,16-Dimethylprostaglandin E2