Cromolyn sodium and masitinib combination inhibits fibroblast-myofibroblast transition and exerts additive cell-protective and antioxidant effects on a bleomycin-induced in vitro fibrosis model
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Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
John Wiley & Sons Ltd
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. While recent studies have suggested the potential efficacy of tyrosine kinase inhibitors in managing IPF, masitinib, a clinically used tyrosine kinase inhibitor, has not yet been investigated for its efficacy in fibrotic lung diseases. In a previous study on an in vitro neurodegenerative model, we demonstrated the synergistic antitoxic and antioxidant effects of masitinib combined with cromolyn sodium, an FDA-approved mast cell stabilizer. This study aims to investigate the anti-fibrotic and antioxidant effects of the masitinib-cromolyn sodium combination in an in vitro model of pulmonary fibrosis. Fibroblast cell cultures treated with bleomycin and/or hydrogen peroxide (H2O2) were subjected to masitinib and/or cromolyn sodium, followed by assessments of cell viability, morphological and apoptotic nuclear changes, triple-immunofluorescence labeling, and total oxidant/antioxidant capacities, besides ratio of Bax and Bcl-2 mRNA expressions as an indication of apoptosis. The combined treatment of masitinib and cromolyn sodium effectively prevented the fibroblast myofibroblast transition, a hallmark of fibrosis, and significantly reduced bleomycin / H2O2-induced apoptosis and oxidative stress. This study is the first to demonstrate the additive anti-fibrotic, cell-protective, and antioxidant effects of the masitinib-cromolyn sodium combination in an in vitro fibrosis model, suggesting its potential as an innovative therapeutic approach for pulmonary fibrosis. Combination therapy may be more advantageous in that both drugs could be administered in lower doses, exerting less side effects, and at the same time providing diverse mechanisms of action simultaneously. Illustration of the Anti-Fibrotic and Antioxidant Effects of Masitinib and Cromolyn Sodium in a Pulmonary Fibrosis ModelThis graphical abstract presents an overview of the experimental design and methodologies used to investigate the anti-fibrotic and antioxidant effects of masitinib and cromolyn sodium in a bleomycin/H2O2-induced pulmonary fibrosis model. Fibroblast cultures were treated with bleomycin and/or H2O2 24 hours after the experiment began, followed by the application of masitinib and/or cromolyn sodium 48 hours later. Multiple assessments-including cell viability assays, morphological evaluation, nuclear DNA staining, immunofluorescence staining, measurements of total oxidant and antioxidant capacities, and analysis of Bax/Bcl-2 mRNA expression levels-were performed to evaluate the effects on fibroblast-to-myofibroblast transition, apoptosis, and oxidative stress.image
Açıklama
Anahtar Kelimeler
Bleomycin, cell culture, Cromolyn sodium, fibroblast, fibroblast-myofibroblast transition, idiopathic pulmonary fibrosis, Masitinib
Kaynak
Pharmacology Research & Perspectives
WoS Q Değeri
Q3
Scopus Q Değeri
Q1
Cilt
12
Sayı
5
