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Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival...

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Autores principales: Ruscitti, Francesca, Ravanetti, Francesca, Bertani, Valeria, Ragionieri, Luisa, Mecozzi, Laura, Sverzellati, Nicola, Silva, Mario, Ruffini, Livia, Menozzi, Valentina, Civelli, Maurizio, Villetti, Gino, Stellari, Franco Fabio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385278/
https://www.ncbi.nlm.nih.gov/pubmed/32792953
http://dx.doi.org/10.3389/fphar.2020.01117
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author Ruscitti, Francesca
Ravanetti, Francesca
Bertani, Valeria
Ragionieri, Luisa
Mecozzi, Laura
Sverzellati, Nicola
Silva, Mario
Ruffini, Livia
Menozzi, Valentina
Civelli, Maurizio
Villetti, Gino
Stellari, Franco Fabio
author_facet Ruscitti, Francesca
Ravanetti, Francesca
Bertani, Valeria
Ragionieri, Luisa
Mecozzi, Laura
Sverzellati, Nicola
Silva, Mario
Ruffini, Livia
Menozzi, Valentina
Civelli, Maurizio
Villetti, Gino
Stellari, Franco Fabio
author_sort Ruscitti, Francesca
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed in vivo for 28 days after BLM administration by micro-computed tomography and ex vivo by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced ex vivo histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable in vivo technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates.
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spelling pubmed-73852782020-08-12 Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography Ruscitti, Francesca Ravanetti, Francesca Bertani, Valeria Ragionieri, Luisa Mecozzi, Laura Sverzellati, Nicola Silva, Mario Ruffini, Livia Menozzi, Valentina Civelli, Maurizio Villetti, Gino Stellari, Franco Fabio Front Pharmacol Pharmacology Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed in vivo for 28 days after BLM administration by micro-computed tomography and ex vivo by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced ex vivo histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable in vivo technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates. Frontiers Media S.A. 2020-07-21 /pmc/articles/PMC7385278/ /pubmed/32792953 http://dx.doi.org/10.3389/fphar.2020.01117 Text en Copyright © 2020 Ruscitti, Ravanetti, Bertani, Ragionieri, Mecozzi, Sverzellati, Silva, Ruffini, Menozzi, Civelli, Villetti and Stellari http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Ruscitti, Francesca
Ravanetti, Francesca
Bertani, Valeria
Ragionieri, Luisa
Mecozzi, Laura
Sverzellati, Nicola
Silva, Mario
Ruffini, Livia
Menozzi, Valentina
Civelli, Maurizio
Villetti, Gino
Stellari, Franco Fabio
Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title_full Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title_fullStr Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title_full_unstemmed Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title_short Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography
title_sort quantification of lung fibrosis in ipf-like mouse model and pharmacological response to treatment by micro-computed tomography
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385278/
https://www.ncbi.nlm.nih.gov/pubmed/32792953
http://dx.doi.org/10.3389/fphar.2020.01117
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