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It is promoted by overproliferation of fibroblasts characterized by the progressive formation of scar tissue in the lung parenchyma, which leads to an inexorable decline in lung function, respiratory failure, and high mortality. This study aims to assess the synergetic consequences of metformin and stearic acid, whether individually or in combination, to ameliorate bleomycin\u2010induced PF in rat models via suppressing Gal\u20103\/Smad3\/\u03b1\u2010SMA and TNF\u2010\u03b1\/NF\u2010\u03ba\u03b2 signaling pathways and mitigate its adverse side effect on kidneys and liver. The antioxidant\/oxidative stress shuttle system was estimated in lung, liver, and kidney tissues. Moreover, histopathology assessment and immunohistochemical staining for NF\u2010\u03ba\u03b2 antibodies were performed in the lung and trachea tissues. Additionally, RT\u2010qPCR gene expressions of TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106, and \u03b1\u2010SMA were investigated. The expression levels of Gal\u20103,\n                    <jats:italic>p<\/jats:italic>\n                    \u2010Gal\u20103, Smad3, and\n                    <jats:italic>p<\/jats:italic>\n                    \u2010Smad3 protein in lung tissues were determined by western blot analysis. The findings showed that metformin and\/or stearic acid exhibited antifibrotic and anti\u2010inflammatory impacts in\u2010vivo as evidenced by enhanced body weight, liver and kidney functions, reduced oxidative stress, increased endogenous antioxidant enzymes, downregulated inflammatory cytokine levels IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1, and attenuation effect on \u03b1\u2010SMA, a major marker of myofibroblasts. Furthermore, there was a marked improvement in the profibrotic Gal\u20103\/Smad3 signaling pathway. On the other hand, a significant reduction in the histological score of fibrosis and immunohistochemical expression NF\u2010\u03ba\u03b2 levels was detected, especially in the combination\u2010treated group. Overall, our findings elucidate the synergetic antifibrotic impact of metformin and stearic acid which could be used as a potential candidate drug against various chronic inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70494","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T15:55:32Z","timestamp":1757951732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Mitigated Effect of the Combination of Metformin and Stearic Acid to Ameliorate Bleomycin\u2010Induced Pulmonary Fibrosis in Rats via Inhibiting Gal\u20103\/Smad3\/\u03b1\u2010SMA and TNF\u2010\u03b1\/NF\u2010\u03ba\u03b2 Signaling Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-6932","authenticated-orcid":false,"given":"Maha M.","family":"Salem","sequence":"first","affiliation":[{"name":"Chemistry Department, Biochemistry Division, Faculty of Science Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermin S.","family":"Youssef","sequence":"additional","affiliation":[{"name":"Chemistry Department, Biochemistry Division, Faculty of Science Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"El Keiy","sequence":"additional","affiliation":[{"name":"Chemistry Department, Biochemistry Division, Faculty of Science Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5216-2712","authenticated-orcid":false,"given":"Abeer A.","family":"Khamis","sequence":"additional","affiliation":[{"name":"Chemistry Department, Biochemistry Division, Faculty of Science Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_12_2_1","article-title":"Idiopathic Pulmonary Fibrosis in a Young Adult: A Rare Presentation and Management Challenges","volume":"15","author":"Saeed S.","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108870"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-021-02113-y"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107608"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","unstructured":"I.Ramli T.Cheriet A. 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