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Cited by 114Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisPhosphodiesterase function and regulationPulmonary Hypertension Research and Treatments

Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin‐induced lung injury

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Cortijo, J, Iranzo, A, Milara, X, Mata, M, Cerdá‐Nicolás, M, Ruiz‐Saurí, A, Tenor, H, Hatzelmann, A +1 more·2009·British Journal of Pharmacology
DOI 10.1111/j.1476-5381.2008.00041.xPMC PMC2697678
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Abstract

Mandarin translation of abstract: Background and purpose: The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin‐induced lung injury were explored in ‘preventive’ and ‘t herapeutic’ protocols and compared with glucocorticoids. Experimental approach: Roflumilast (1 and 5 mg·kg−1·d−1, p.o.) or dexamethasone (2.5 mg·kg−1·d−1, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg−1). In Wistar rats, roflumilast (1 mg·kg−1·d−1, p.o.) was compared with methylprednisolone (10 mg·kg−1·d−1, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillation of bleomycin (7.5 U·kg−1). Analyses were performed at the end of the treatment periods. Key results: Preventive. Roflumilast reduced bleomycin‐induced lung hydroxyproline, lung fibrosis and right ventricular hypertrophy; muscularization of intraacinar pulmonary vessels was also attenuated. The PDE4 inhibitor diminished bleomycin‐induced transcripts for tumour necrosis factor (TNFα), transforming growth factor (TGFβ), connective tissue growth factor, αI(I)collagen, endothelin‐1 and the mucin, Muc5ac, in lung, and reduced bronchoalveolar lavage fluid levels of TNFα, interleukin‐13, TGFβ, Muc5ac, lipid hydroperoxides and inflammatory cell counts.Therapeutic. In mice, roflumilast but not dexamethasone reduced bleomycin‐induced lung αI(I)collagen transcripts, fibrosis and right ventricular hypertrophy. Similar results were found in the rat. Conclusions and implications: Roflumilast prevented the development of bleomycin‐induced lung injury, and alleviated the lung fibrotic and vascular remodeling response to bleomycin in a therapeutic protocol, the latter being resistant to glucocorticoids. Mandarin translation of abstract

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Authors
Cortijo, J., Iranzo, A., Milara, X., Mata, M., Cerdá‐Nicolás, M., Ruiz‐Saurí, A., Tenor, H., Hatzelmann, A., & Morcillo, E.
Affiliations
Universitat de València (ES)
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2009-02
Volume
156
Issue
3
Pages
534-544
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/j.1476-5381.2008.00041.x
PMC
PMC2697678
OpenAlex
W2026501434
Cited by
114
References
1
Citations by year
2026: 5 · 2025: 8 · 2024: 16 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 9 · 2012: 6
FWCI
6.19
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Generalitat Valenciana (CB06/06/0027)
  • Ministerio de Ciencia e Innovación (CB06/06/0027)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
roflumilast, phosphodiesterase-4 inhibitors, bleomycin-induced lung injury, pulmonary fibrosis, vascular remodeling, glucocorticoid resistance, dexamethasone, methylprednisolone, TNF-α, TGF-beta, MUC5AC, collagen deposition, right ventricular hypertrophy, bleomycin pneumonitis, anti-inflammatory therapy
MeSH terms
Aminopyridines, Animals, Benzamides, Bleomycin, Bronchoalveolar Lavage Fluid, Cyclopropanes, Disease Models, Animal, Lung, Male, Mice, Inbred C57BL, Phosphodiesterase Inhibitors, Pulmonary Fibrosis, Rats, Wistar, Bronchoalveolar Lavage, Reverse Transcriptase Polymerase Chain Reaction, Mice, Rats, Lung Injury, Phosphodiesterase 4 Inhibitors

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