Effect of preventive or therapeutic treatment with angiotensin 1–7 in a model of bleomycin-induced lung fibrosis in mice
| Autor: | Flávia Rago, Eliza Mathias Melo, Mauro M. Teixeira, Geovanni Dantas Cassali, Lucas Kraemer, Robson A.S. Santos, Remo Castro Russo, Izabela Galvão |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Pulmonary Fibrosis Immunology Inflammation Context (language use) Pharmacology Biology Bleomycin 03 medical and health sciences Idiopathic pulmonary fibrosis chemistry.chemical_compound 0302 clinical medicine Fibrosis Oral administration Pulmonary fibrosis medicine Animals Immunology and Allergy Lung Therapeutic effect Cell Biology medicine.disease Survival Analysis Peptide Fragments Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry 030220 oncology & carcinogenesis Leukocytes Mononuclear Angiotensin I medicine.symptom |
| Zdroj: | Journal of Leukocyte Biology. 106:677-686 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | Idiopathic pulmonary fibrosis is characterized by aberrant fibroblast activation and excessive collagen deposition that may eventually lead to organ dysfunction. Lung fibrosis is frequently observed in cancer patients undergoing bleomycin (BLM) treatment. Therefore, BLM instillation in mice is the most frequent model used to investigate pulmonary fibrosis. Angiotensin 1–7 [Ang-(1-7)] is a heptapeptide with anti-inflammatory and proresolving activity. Here, we studied the effects of preventive and therapeutic oral administration of Ang-(1-7) in a model of BLM-induced lung fibrosis in mice. Male C57Bl/6j mice were instilled with BLM and followed for weight loss and survival or euthanized to examine pulmonary inflammation, fibrosis, and lung function. For preventive treatment, mice were treated with Ang-(1-7) 1 h before instillation and then twice daily. We observed that preventive treatment with Ang-(1-7) decreased weight loss, inflammation and collagen deposition, increased survival, and ameliorated lung function. Therapeutic treatment with Ang-(1-7), starting 3 days after BLM instillation resulted in decreased inflammation, decreased collagen deposition, and ameliorated lung function, although the effects were of lower magnitude than the preventive treatment. Therapeutic treatment with Ang-(1-7) starting 7 or 14 days after BLM instillation failed to alter any of the changes observed. Therefore, although oral preventive treatment with Ang-(1-7) is effective to decrease pulmonary inflammation, fibrosis, and functional changes induced by BLM, therapeutic effects are much less significant, arguing against its use in patients with chronic fibrosis. It remains to be determined whether other proresolving molecules will have better therapeutic effects in the context of chronic pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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