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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\u00a0vitro neurodegenerative model, we demonstrated the synergistic antitoxic and antioxidant effects of masitinib combined with cromolyn sodium, an FDA\u2010approved mast cell stabilizer. This study aims to investigate the anti\u2010fibrotic and antioxidant effects of the masitinib\u2010cromolyn sodium combination in an in\u00a0vitro model of pulmonary fibrosis. Fibroblast cell cultures treated with bleomycin and\/or hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) were subjected to masitinib and\/or cromolyn sodium, followed by assessments of cell viability, morphological and apoptotic nuclear changes, triple\u2010immunofluorescence labeling, and total oxidant\/antioxidant capacities, besides ratio of Bax and Bcl\u20102 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 \/ H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced apoptosis and oxidative stress. This study is the first to demonstrate the additive anti\u2010fibrotic, cell\u2010protective, and antioxidant effects of the masitinib\u2010cromolyn sodium combination in an in\u00a0vitro 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.<\/jats:p>","DOI":"10.1002\/prp2.70018","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T09:39:42Z","timestamp":1727948382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cromolyn sodium and masitinib combination inhibits fibroblast\u2010myofibroblast transition and exerts additive cell\u2010protective and antioxidant effects on a bleomycin\u2010induced in\u00a0vitro fibrosis model"],"prefix":"10.1002","volume":"12","author":[{"given":"Azize Yasemin","family":"G\u00f6ksu","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology Akdeniz University, School of Medicine  Antalya Turkey"},{"name":"Department of Gene and Cell Therapy Akdeniz University, School of Medicine  Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hulya","family":"Dirol","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases Akdeniz University, School of Medicine  Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Gonca","family":"Kocanci","sequence":"additional","affiliation":[{"name":"Vocational High School of Health Services, Department of Medical Laboratory Techniques Alanya Alaaddin Keykubat University  Alanya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107798"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2007.02.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652406777435426"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0366-6999.2000.09.102"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.6.8520779"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2004.03.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00174914"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.55.5272"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(18)30502-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-6618(02)00122-6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2017"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007258"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0620-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31403-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.381"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200404-531OC"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.26.6.675"},{"issue":"2","key":"e_1_2_12_20_1","first-page":"185","article-title":"The pathogenesis of Bleomycin\u2010induced pulmonary fibrosis in mice","volume":"77","author":"Adamson IYR","year":"1974","journal-title":"Am J Pathol"},{"issue":"1","key":"e_1_2_12_21_1","first-page":"117","article-title":"Bleomycin\u2010induced pulmonary fibrosis in the rat: inhibition by indomethacin","volume":"95","author":"Thrall RS","year":"1979","journal-title":"Am J Pathol"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr980449z"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00442a003"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112695"},{"issue":"6","key":"e_1_2_12_25_1","first-page":"1754","article-title":"Rat alveolar myofibroblasts acquire alpha\u2010smooth muscle actin expression during bleomycin\u2010induced pulmonary fibrosis","volume":"143","author":"Vyalov SL","year":"1993","journal-title":"Am J Pathol"},{"issue":"1","key":"e_1_2_12_26_1","first-page":"114","article-title":"Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. 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