{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:20:47Z","timestamp":1778685647612,"version":"3.51.4"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Science, Technology & Innovation Funding Authority"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cilostazol, a selective phosphodiesterase type III inhibitor, enhances intracellular cAMP and exhibits potent antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effect of cilostazol (50\u00a0mg\/kg\/day, orally) against amiodarone (AMIO)-induced pulmonary fibrosis (PF) and to elucidate its underlying mechanisms. Lung index as well as total and differential cell counts in bronchoalveolar lavage fluid (BALF) were estimated. Histopathological changes were evaluated using hematoxylin and eosin (H&amp;E) and Masson\u2019s trichrome staining. Malondialdehyde (MDA) and glutathione (GSH) contents were assessed colorimetrically, while TNF-\u03b1, IL-1\u03b2, and cAMP levels in the lungs were determined using ELISA. TGF-\u03b21 and vimentin expressions were examined immunohistochemically, SIRT1 protein expression by Western blotting, and EPAC1 gene expression by RT-PCR. AMIO administration caused significant increases in lung index, inflammatory cytokines, oxidative stress markers, and fibrotic mediators, accompanied by a decline in GSH and cAMP levels and severe histopathological damage. Cilostazol co-treatment markedly attenuated these alterations, decreasing TNF-\u03b1, IL-1\u03b2, MDA, TGF-\u03b21, and vimentin while restoring GSH, cAMP, SIRT1, and EPAC1 expressions and improving lung architecture. Cilostazol mitigates AMIO-induced PF through attenuation of oxidative stress, inflammation, and EMT, potentially via activation of the SIRT1\/EPAC1\/cAMP pathway. These findings highlight cilostazol as a promising therapeutic adjunct against drug-induced PF.<\/jats:p>","DOI":"10.1038\/s41598-026-45341-3","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:45:57Z","timestamp":1778683557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cilostazol mitigates amiodarone-induced pulmonary toxicity and fibrosis by regulating the cAMP\/TGF-\u03b21 pathway-mediated epithelial-to-mesenchymal transition in rats"],"prefix":"10.1038","volume":"16","author":[{"given":"Mohamad A.","family":"El-Gammal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman H.","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed G.","family":"Abd Elhameed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed M.","family":"Salama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammed M.","family":"Salahuddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"45341_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0643-3","volume":"18","author":"P Faverio","year":"2018","unstructured":"Faverio, P. et al. Management of acute respiratory failure in interstitial lung diseases: Overview and clinical insights. BMC Pulm. Med. 18, 70 (2018).","journal-title":"BMC Pulm. Med."},{"key":"45341_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trsl.2019.02.001","volume":"209","author":"SK Mathai","year":"2019","unstructured":"Mathai, S. K. & Schwartz, D. A. Translational research in pulmonary fibrosis. Transl. Res. 209, 1\u201313 (2019).","journal-title":"Transl. Res."},{"key":"45341_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7080201","volume":"7","author":"SL Barratt","year":"2018","unstructured":"Barratt, S. L., Creamer, A., Hayton, C. & Chaudhuri, N. Idiopathic pulmonary fibrosis (IPF): An overview. J. Clin. Med. 7, 201 (2018).","journal-title":"J. Clin. Med."},{"key":"45341_CR4","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.1513\/AnnalsATS.201410-448MG","volume":"12","author":"RC Chambers","year":"2015","unstructured":"Chambers, R. C. & Mercer, P. F. Mechanisms of alveolar epithelial injury, repair, and fibrosis. Ann. Am. Thorac. Soc. 12, S16\u2013S20 (2015).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"45341_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107798","volume":"222","author":"P Spagnolo","year":"2021","unstructured":"Spagnolo, P. et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol. Ther. 222, 107798 (2021).","journal-title":"Pharmacol. Ther."},{"key":"45341_CR6","doi-asserted-by":"publisher","first-page":"L675","DOI":"10.1152\/ajplung.00258.2020","volume":"319","author":"JH Lipinski","year":"2020","unstructured":"Lipinski, J. H., Moore, B. B. & O\u2019Dwyer, D. N. The evolving role of the lung microbiome in pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 319, L675\u2013L682 (2020).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"45341_CR7","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1248\/bpb.b24-00534","volume":"47","author":"B Bian","year":"2024","unstructured":"Bian, B. et al. Wogonin attenuates bleomycin-induced pulmonary fibrosis and oxidative stress injury via the MAPK signaling pathway. Biol. Pharm. Bull. 47, 2165\u20132172 (2024).","journal-title":"Biol. Pharm. Bull."},{"key":"45341_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116691","volume":"315","author":"H Shi","year":"2023","unstructured":"Shi, H. et al. Network pharmacology and experiments in vivo and in vitro reveal that the Jia-Wei-Bu-Shen-Yi-Qi formula (JWBSYQF) and its active ingredient baicalein ameliorate BLM-induced lung fibrosis in mice via PI3K\/Akt signaling pathway. J. Ethnopharmacol. 315, 116691 (2023).","journal-title":"J. Ethnopharmacol."},{"key":"45341_CR9","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/S2213-2600(14)70101-8","volume":"2","author":"G Raghu","year":"2014","unstructured":"Raghu, G. et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: Incidence, prevalence, and survival, 2001\u201311. Lancet. Respir. Med. 2, 566\u2013572 (2014).","journal-title":"Lancet. Respir. Med."},{"key":"45341_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01791-z","volume":"22","author":"TM Maher","year":"2021","unstructured":"Maher, T. M. et al. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir. Res. 22, 197 (2021).","journal-title":"Respir. Res."},{"key":"45341_CR11","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1183\/09031936.00185114","volume":"46","author":"J Hutchinson","year":"2015","unstructured":"Hutchinson, J., Fogarty, A., Hubbard, R. & McKeever, T. Global incidence and mortality of idiopathic pulmonary fibrosis: A systematic review. Eur. Respir. J. 46, 795\u2013806 (2015).","journal-title":"Eur. Respir. J."},{"key":"45341_CR12","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMra1705751","volume":"378","author":"DJ Lederer","year":"2018","unstructured":"Lederer, D. J. & Martinez, F. J. Idiopathic pulmonary fibrosis. N. Engl. J. Med. 378, 1811\u20131823 (2018).","journal-title":"N. Engl. J. Med."},{"key":"45341_CR13","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1183\/09059180.00001013","volume":"22","author":"J Behr","year":"2013","unstructured":"Behr, J. Evidence-based treatment strategies in idiopathic pulmonary fibrosis. Eur. Respir. Rev. 22, 163\u2013168 (2013).","journal-title":"Eur. Respir. Rev."},{"key":"45341_CR14","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2165\/00003495-199243010-00007","volume":"43","author":"J Gill","year":"1992","unstructured":"Gill, J., Heel, R. C. & Fitton, A. Amiodarone. An overview of its pharmacological properties, and review of its therapeutic use in cardiac arrhythmias. Drugs 43, 69\u2013110. https:\/\/doi.org\/10.2165\/00003495-199243010-00007 (1992).","journal-title":"Drugs"},{"key":"45341_CR15","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1038\/sj.bjp.0705362","volume":"139","author":"D Punithavathi","year":"2003","unstructured":"Punithavathi, D., Venkatesan, N. & Babu, M. Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats. Br. J. Pharmacol. 139, 1342\u20131350. https:\/\/doi.org\/10.1038\/sj.bjp.0705362 (2003).","journal-title":"Br. J. Pharmacol."},{"key":"45341_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-12-76","volume":"12","author":"A Andersson-Sj\u00f6land","year":"2011","unstructured":"Andersson-Sj\u00f6land, A., Nihlberg, K., Eriksson, L., Bjermer, L. & Westergren-Thorsson, G. Fibrocytes and the tissue niche in lung repair. Respir. Res. 12, 76. https:\/\/doi.org\/10.1186\/1465-9921-12-76 (2011).","journal-title":"Respir. Res."},{"key":"45341_CR17","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.yexcr.2017.05.028","volume":"357","author":"R Tian","year":"2017","unstructured":"Tian, R. et al. NLRP3 participates in the regulation of EMT in bleomycin-induced pulmonary fibrosis. Exp. Cell Res. 357, 328\u2013334. https:\/\/doi.org\/10.1016\/j.yexcr.2017.05.028 (2017).","journal-title":"Exp. Cell Res."},{"key":"45341_CR18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","volume":"166","author":"MA Nieto","year":"2016","unstructured":"Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016. Cell 166, 21\u201345. https:\/\/doi.org\/10.1016\/j.cell.2016.06.028 (2016).","journal-title":"Cell"},{"key":"45341_CR19","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.pharmthera.2017.08.009","volume":"182","author":"M Singh","year":"2018","unstructured":"Singh, M., Yelle, N., Venugopal, C. & Singh, S. K. EMT: Mechanisms and therapeutic implications. Pharmacol. Ther. 182, 80\u201394. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.08.009 (2018).","journal-title":"Pharmacol. Ther."},{"key":"45341_CR20","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nrm3758","volume":"15","author":"S Lamouille","year":"2014","unstructured":"Lamouille, S., Xu, J. & Derynck, R. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15, 178\u2013196. https:\/\/doi.org\/10.1038\/nrm3758 (2014).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"45341_CR21","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1083\/jcb.200601018","volume":"172","author":"JM Lee","year":"2006","unstructured":"Lee, J. M., Dedhar, S., Kalluri, R. & Thompson, E. W. The epithelial-mesenchymal transition: New insights in signaling, development, and disease. J. Cell Biol. 172, 973\u2013981. https:\/\/doi.org\/10.1083\/jcb.200601018 (2006).","journal-title":"J. Cell Biol."},{"key":"45341_CR22","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.3892\/or.2016.4964","volume":"36","author":"WJ Sung","year":"2016","unstructured":"Sung, W. J., Kim, H. & Park, K. K. The biological role of epithelial-mesenchymal transition in lung cancer (Review). Oncol. Rep. 36, 1199\u20131206. https:\/\/doi.org\/10.3892\/or.2016.4964 (2016).","journal-title":"Oncol. Rep."},{"key":"45341_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9080101","author":"A Legras","year":"2017","unstructured":"Legras, A. et al. Epithelial-to-mesenchymal transition and MicroRNAs in lung cancer. Cancers https:\/\/doi.org\/10.3390\/cancers9080101 (2017).","journal-title":"Cancers"},{"key":"45341_CR24","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1513\/pats.200601-004TK","volume":"3","author":"BC Willis","year":"2006","unstructured":"Willis, B. C., duBois, R. M. & Borok, Z. Epithelial origin of myofibroblasts during fibrosis in the lung. Proc. Am. Thorac. Soc. 3, 377\u2013382. https:\/\/doi.org\/10.1513\/pats.200601-004TK (2006).","journal-title":"Proc. Am. Thorac. Soc."},{"key":"45341_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-120","volume":"14","author":"SS Sohal","year":"2013","unstructured":"Sohal, S. S. & Walters, E. H. Role of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD). Respir. Res. 14, 120. https:\/\/doi.org\/10.1186\/1465-9921-14-120 (2013).","journal-title":"Respir. Res."},{"key":"45341_CR26","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/labinvest.2015.114","volume":"95","author":"HR Jonsdottir","year":"2015","unstructured":"Jonsdottir, H. R. et al. Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture. Lab. Invest. 95, 1418\u20131428. https:\/\/doi.org\/10.1038\/labinvest.2015.114 (2015).","journal-title":"Lab. Invest."},{"key":"45341_CR27","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1002\/dvdy.24541","volume":"247","author":"MK Jolly","year":"2018","unstructured":"Jolly, M. K. et al. Epithelial-mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease. Dev. Dyn. 247, 346\u2013358. https:\/\/doi.org\/10.1002\/dvdy.24541 (2018).","journal-title":"Dev. Dyn."},{"key":"45341_CR28","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/path.3016","volume":"226","author":"L DeMaio","year":"2012","unstructured":"DeMaio, L. et al. Ligand-independent Transforming growth factor-\u03b2 Type I receptor signalling mediates Type I collagen-induced epithelial-mesenchymal transition. J. Pathol. 226, 633\u2013644. https:\/\/doi.org\/10.1002\/path.3016 (2012).","journal-title":"J. Pathol."},{"key":"45341_CR29","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/labinvest.2016.135","volume":"97","author":"M Yamaguchi","year":"2017","unstructured":"Yamaguchi, M. et al. Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis. Lab. Invest. 97, 232\u2013242. https:\/\/doi.org\/10.1038\/labinvest.2016.135 (2017).","journal-title":"Lab. Invest."},{"key":"45341_CR30","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.prp.2011.06.006","volume":"207","author":"P Morbini","year":"2011","unstructured":"Morbini, P. et al. Incomplete expression of epithelial-mesenchymal transition markers in idiopathic pulmonary fibrosis. Pathol. Res. Pract. 207, 559\u2013567. https:\/\/doi.org\/10.1016\/j.prp.2011.06.006 (2011).","journal-title":"Pathol. Res. Pract."},{"key":"45341_CR31","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1136\/thoraxjnl-2013-204608","volume":"69","author":"D Bartis","year":"2014","unstructured":"Bartis, D., Mise, N., Mahida, R. Y., Eickelberg, O. & Thickett, D. R. Epithelial-mesenchymal transition in lung development and disease: Does it exist and is it important?. Thorax 69, 760\u2013765. https:\/\/doi.org\/10.1136\/thoraxjnl-2013-204608 (2014).","journal-title":"Thorax"},{"key":"45341_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2017.09.002","volume":"183","author":"S Jansen","year":"2018","unstructured":"Jansen, S., Gosens, R., Wieland, T. & Schmidt, M. Paving the Rho in cancer metastasis: Rho GTPases and beyond. Pharmacol. Ther. 183, 1\u201321. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.09.002 (2018).","journal-title":"Pharmacol. Ther."},{"key":"45341_CR33","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1002\/1878-0261.12083","volume":"11","author":"MK Jolly","year":"2017","unstructured":"Jolly, M. K., Ware, K. E., Gilja, S., Somarelli, J. A. & Levine, H. EMT and MET: Necessary or permissive for metastasis?. Mol. Oncol. 11, 755\u2013769. https:\/\/doi.org\/10.1002\/1878-0261.12083 (2017).","journal-title":"Mol. Oncol."},{"key":"45341_CR34","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1476-5381.2012.01847.x","volume":"166","author":"PA Insel","year":"2012","unstructured":"Insel, P. A. et al. cAMP and Epac in the regulation of tissue fibrosis. Br. J. Pharmacol. 166, 447\u2013456. https:\/\/doi.org\/10.1111\/j.1476-5381.2012.01847.x (2012).","journal-title":"Br. J. Pharmacol."},{"key":"45341_CR35","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev.pharmtox.010909.105714","volume":"50","author":"M Gloerich","year":"2010","unstructured":"Gloerich, M. & Bos, J. L. Epac: Defining a new mechanism for cAMP action. Annu. Rev. Pharmacol. Toxicol. 50, 355\u2013375. https:\/\/doi.org\/10.1146\/annurev.pharmtox.010909.105714 (2010).","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"45341_CR36","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/j.1476-5381.2009.00458.x","volume":"159","author":"M Grandoch","year":"2010","unstructured":"Grandoch, M., Roscioni, S. S. & Schmidt, M. The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function. Br. J. Pharmacol. 159, 265\u2013284. https:\/\/doi.org\/10.1111\/j.1476-5381.2009.00458.x (2010).","journal-title":"Br. J. Pharmacol."},{"key":"45341_CR37","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.cellsig.2011.03.007","volume":"23","author":"M Breckler","year":"2011","unstructured":"Breckler, M. et al. Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications. Cell. Signal. 23, 1257\u20131266 (2011).","journal-title":"Cell. Signal."},{"key":"45341_CR38","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.tibs.2006.10.002","volume":"31","author":"JL Bos","year":"2006","unstructured":"Bos, J. L. Epac proteins: multi-purpose cAMP targets. Trends Biochem. Sci. 31, 680\u2013686. https:\/\/doi.org\/10.1016\/j.tibs.2006.10.002 (2006).","journal-title":"Trends Biochem. Sci."},{"key":"45341_CR39","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.cellsig.2007.07.009","volume":"20","author":"GG Holz","year":"2008","unstructured":"Holz, G. G., Chepurny, O. G. & Schwede, F. Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors. Cell. Signal. 20, 10\u201320. https:\/\/doi.org\/10.1016\/j.cellsig.2007.07.009 (2008).","journal-title":"Cell. Signal."},{"key":"45341_CR40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1053\/jscd.2000.7216","volume":"9","author":"F Gotoh","year":"2000","unstructured":"Gotoh, F. et al. Cilostazol stroke prevention study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J. Stroke Cerebrovasc. Dis. 9, 147\u2013157 (2000).","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"45341_CR41","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/j.1527-3466.2001.tb00076.x","volume":"19","author":"Y Liu","year":"2001","unstructured":"Liu, Y., Shakur, Y., Yoshitake, M. & Kambayashi, J. i. Cilostazol (Pletal\u00ae): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc. Drug Rev. 19, 369\u2013386 (2001).","journal-title":"Cardiovasc. Drug Rev."},{"key":"45341_CR42","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1159\/000135654","volume":"26","author":"Y Shinohara","year":"2008","unstructured":"Shinohara, Y. et al. Antiplatelet cilostazol is beneficial in diabetic and\/or hypertensive ischemic stroke patients: subgroup analysis of the cilostazol stroke prevention study. Cerebrovasc. Dis. 26, 63\u201370 (2008).","journal-title":"Cerebrovasc. Dis."},{"key":"45341_CR43","doi-asserted-by":"publisher","unstructured":"Rondina, M. T. & Weyrich, A. S. Targeting phosphodiesterases in anti-platelet therapy. In Handbook of Experimental Pharmacology 225\u2013238 (2012). https:\/\/doi.org\/10.1007\/978-3-642-29423-5_9.","DOI":"10.1007\/978-3-642-29423-5_9"},{"key":"45341_CR44","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/cvr\/cvn226","volume":"81","author":"Y Hattori","year":"2009","unstructured":"Hattori, Y. et al. Cilostazol inhibits cytokine-induced nuclear factor-\u03baB activation via AMP-activated protein kinase activation in vascular endothelial cells. Cardiovasc. Res. 81, 133\u2013139 (2009).","journal-title":"Cardiovasc. Res."},{"key":"45341_CR45","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1080\/15376516.2018.1528648","volume":"29","author":"HM Hafez","year":"2019","unstructured":"Hafez, H. M., Ibrahim, M. A., Zedan, M. Z., Hassan, M. & Hassanein, H. Nephroprotective effect of Cilostazol and Verapamil against thioacetamide-induced toxicity in rats may involve Nrf2\/HO-1\/NQO-1 signaling pathway. Toxicol. Mech. Methods. 29, 146\u2013152. https:\/\/doi.org\/10.1080\/15376516.2018.1528648 (2019).","journal-title":"Toxicol. Mech. Methods."},{"key":"45341_CR46","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1080\/15376516.2020.1774829","volume":"30","author":"AM Abdel-Aziz","year":"2020","unstructured":"Abdel-Aziz, A. M., Mohamed, A. S. M., Abdelazem, O., Okasha, A. M. M. & Kamel, M. Y. Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: Role of cAMP and HO-1. Toxicol. Mech. Methods. 30, 526\u2013535 (2020).","journal-title":"Toxicol. Mech. Methods."},{"key":"45341_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173234","volume":"881","author":"SM Elshazly","year":"2020","unstructured":"Elshazly, S. M., Elhassanny, A. E. & Mahmoud, N. M. Cilostazol protects against acetic acid-induced colitis in rats: Possible role for cAMP\/SIRT1 pathway. Eur. J. Pharmacol. 881, 173234 (2020).","journal-title":"Eur. J. Pharmacol."},{"key":"45341_CR48","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/hepr.12140","volume":"44","author":"S Saito","year":"2014","unstructured":"Saito, S. et al. Cilostazol attenuates hepatic stellate cell activation and protects mice against carbon tetrachloride-induced liver fibrosis. Hepatol. Res. 44, 460\u2013473 (2014).","journal-title":"Hepatol. Res."},{"key":"45341_CR49","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jss.2017.02.020","volume":"213","author":"T Fujii","year":"2017","unstructured":"Fujii, T. et al. Oral administration of Cilostazol improves survival rate after rat liver ischemia\/reperfusion injury. J. Surg. Res. 213, 207\u2013214 (2017).","journal-title":"J. Surg. Res."},{"key":"45341_CR50","doi-asserted-by":"publisher","DOI":"10.5606\/tgkdc.dergisi.2012.110","author":"G \u00d6nem","year":"2012","unstructured":"\u00d6nem, G. Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion. Turk. J. Thorac. Cardiovasc. Surg. https:\/\/doi.org\/10.5606\/tgkdc.dergisi.2012.110 (2012).","journal-title":"Turk. J. Thorac. Cardiovasc. Surg."},{"key":"45341_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-12-113","volume":"12","author":"L Satish","year":"2011","unstructured":"Satish, L., Gallo, P. H., Baratz, M. E., Johnson, S. & Kathju, S. Reversal of TGF-\u03b21 stimulation of \u03b1-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren\u2019s-derived fibroblasts. BMC Musculoskelet. Disord. 12, 113 (2011).","journal-title":"BMC Musculoskelet. Disord."},{"key":"45341_CR52","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.3390\/biom10101433","volume":"10","author":"M Elnagdy","year":"2020","unstructured":"Elnagdy, M., Barve, S., McClain, C. & Gobejishvili, L. cAMP signaling in pathobiology of alcohol associated liver disease. Biomolecules 10, 1433 (2020).","journal-title":"Biomolecules"},{"key":"45341_CR53","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1034\/j.1600-0773.2003.920204.x","volume":"92","author":"BD Uhal","year":"2003","unstructured":"Uhal, B. D. et al. Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists. Pharmacol. Toxicol. 92, 81\u201387 (2003).","journal-title":"Pharmacol. Toxicol."},{"key":"45341_CR54","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/1440-1681.13728","volume":"50","author":"I Harb","year":"2023","unstructured":"Harb, I. et al. Nicorandil mitigates amiodarone-induced pulmonary toxicity and fibrosis in association with the inhibition of lung TGF-\u03b21\/PI3K\/Akt1-p\/mTOR axis in rats. Clin. Exp. Pharmacol. Physiol. 50, 96\u2013106. https:\/\/doi.org\/10.1111\/1440-1681.13728 (2023).","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"45341_CR55","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1007\/s10787-023-01168-2","volume":"31","author":"MM El Tabaa","year":"2023","unstructured":"El Tabaa, M. M., El Tabaa, M. M., Elgharabawy, R. M. & Abdelhamid, W. G. Suppressing NLRP3 activation and PI3K\/AKT\/mTOR signaling ameliorates amiodarone-induced pulmonary fibrosis in rats: A possible protective role of nobiletin. Inflammopharmacology 31, 1373\u20131386. https:\/\/doi.org\/10.1007\/s10787-023-01168-2 (2023).","journal-title":"Inflammopharmacology"},{"key":"45341_CR56","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1080\/10520295.2017.1350750","volume":"92","author":"EM El-Mohandes","year":"2017","unstructured":"El-Mohandes, E. M., Moustafa, A. M., Khalaf, H. A. & Hassan, Y. F. The role of mast cells and macrophages in amiodarone induced pulmonary fibrosis and the possible attenuating role of atorvastatin. Biotechnic Histochem. 92, 467\u2013480. https:\/\/doi.org\/10.1080\/10520295.2017.1350750 (2017).","journal-title":"Biotechnic Histochem."},{"key":"45341_CR57","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1016\/0006-2952(87)90635-6","volume":"36","author":"E Riva","year":"1987","unstructured":"Riva, E. et al. Amiodarone induced phospholipidosis. Biochemical, morphological and functional changes in the lungs of rats chronically treated with amiodarone. Biochem. Pharmacol. 36, 3209\u20133214. https:\/\/doi.org\/10.1016\/0006-2952(87)90635-6 (1987).","journal-title":"Biochem. Pharmacol."},{"key":"45341_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109750","volume":"116","author":"SE Abu-Risha","year":"2023","unstructured":"Abu-Risha, S. E., Sokar, S. S., Elbohoty, H. R. & Elsisi, A. E. Combined carvacrol and cilostazol ameliorate ethanol-induced liver fibrosis in rats: Possible role of SIRT1\/Nrf2\/HO-1 pathway. Int. Immunopharmacol. 116, 109750. https:\/\/doi.org\/10.1016\/j.intimp.2023.109750 (2023).","journal-title":"Int. Immunopharmacol."},{"key":"45341_CR59","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.1007\/s00210-024-03530-9","volume":"398","author":"EH Yousef","year":"2025","unstructured":"Yousef, E. H., El Gayar, A. M. & Abo El-Magd, N. F. Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1\u03b1\/STAT3\/ FGL1 pathway: In silico and in vivo study. Naunyn Schmiedebergs Arch. Pharmacol. 398, 4335\u20134353. https:\/\/doi.org\/10.1007\/s00210-024-03530-9 (2025).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"45341_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-024-02840-1","volume":"24","author":"MA Rajizadeh","year":"2024","unstructured":"Rajizadeh, M. A. et al. Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training. BMC Pulm. Med. 24, 37. https:\/\/doi.org\/10.1186\/s12890-024-02840-1 (2024).","journal-title":"BMC Pulm. Med."},{"key":"45341_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121692","volume":"324","author":"NAT Abbas","year":"2023","unstructured":"Abbas, N. A. T. et al. Repurposing of carvedilol to alleviate bleomycin-induced lung fibrosis in rats: Repressing of TGF-\u03b21\/\u03b1-SMA\/Smad2\/3 and STAT3 gene expressions. Life Sci. 324, 121692. https:\/\/doi.org\/10.1016\/j.lfs.2023.121692 (2023).","journal-title":"Life Sci."},{"issue":"1","key":"45341_CR62","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/s12931-018-0935-4","volume":"19","author":"MR Passmore","year":"2018","unstructured":"Passmore, M. R. et al. Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock. Respir. Res. 19231. (2018).","journal-title":"Respir. Res."},{"key":"45341_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112511","volume":"137","author":"AM El-Dessouki","year":"2024","unstructured":"El-Dessouki, A. M. et al. Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K\/Akt and MAPK\/JNK\/ERK signaling pathways. Int. Immunopharmacol. 137, 112511. https:\/\/doi.org\/10.1016\/j.intimp.2024.112511 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"45341_CR64","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2010).","journal-title":"J. Comput. Chem."},{"key":"45341_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05399-x","volume":"22","author":"TT Liu","year":"2024","unstructured":"Liu, T. T. et al. Bicyclol attenuates pulmonary fibrosis with silicosis via both canonical and non-canonical TGF-\u03b21 signaling pathways. J. Transl. Med. 22, 682. https:\/\/doi.org\/10.1186\/s12967-024-05399-x (2024).","journal-title":"J. Transl. Med."},{"key":"45341_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108889","volume":"115","author":"J Weng","year":"2019","unstructured":"Weng, J. et al. Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1\/2 and p38 MAPK signaling in fibroblasts. Biomed. Pharmacother. 115, 108889. https:\/\/doi.org\/10.1016\/j.biopha.2019.108889 (2019).","journal-title":"Biomed. Pharmacother."},{"key":"45341_CR67","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.3892\/etm.2019.7207","volume":"17","author":"K Han","year":"2019","unstructured":"Han, K., Zhang, Y. & Yang, Z. Cilostazol protects rats against alcohol-induced hepatic fibrosis via suppression of TGF-\u03b21\/CTGF activation and the cAMP\/Epac1 pathway. Exp. Ther. Med. 17, 2381\u20132388. https:\/\/doi.org\/10.3892\/etm.2019.7207 (2019).","journal-title":"Exp. Ther. Med."},{"key":"45341_CR68","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179441","author":"C Delrue","year":"2024","unstructured":"Delrue, C., Speeckaert, R., Moresco, R. N. & Speeckaert, M. M. Cyclic adenosine monophosphate signaling in chronic kidney disease: Molecular targets and therapeutic potentials. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms25179441 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"45341_CR69","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6265853","volume":"2016","author":"B Al-Shammari","year":"2016","unstructured":"Al-Shammari, B., Khalifa, M., Bakheet, S. A. & Yasser, M. A mechanistic study on the amiodarone-induced pulmonary toxicity. Oxid. Med. Cell. Longev. 2016, 6265853. https:\/\/doi.org\/10.1155\/2016\/6265853 (2016).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"45341_CR70","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04568-z","author":"AG El-Waseif","year":"2025","unstructured":"El-Waseif, A. G., Elshal, M., El-Kashef, D. H. & Abu-Elsaad, N. M. Attenuating Amiodarone-induced lung toxicity by the Vitamin D receptor activator paricalcitol in rats: Targeting TLR4\/NF-\u03baB\/HIF-1\u03b1 and TGF-\u03b2\/Smad signaling pathways. Naunyn Schmiedebergs Arch. Pharmacol. https:\/\/doi.org\/10.1007\/s00210-025-04568-z (2025).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"45341_CR71","doi-asserted-by":"publisher","first-page":"4111","DOI":"10.1007\/s00210-024-03450-8","volume":"398","author":"H Farouk","year":"2025","unstructured":"Farouk, H., Moustafa, P. E., Khattab, M. S. & El-Marasy, S. A. Diacerein ameliorates Amiodarone-induced pulmonary fibrosis via targeting the TGF\u03b21\/\u03b1-SMA\/Smad3 pathway. Naunyn Schmiedebergs Arch. Pharmacol. 398, 4111\u20134122. https:\/\/doi.org\/10.1007\/s00210-024-03450-8 (2025).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"45341_CR72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216301","volume":"14","author":"SA El Awdan","year":"2019","unstructured":"El Awdan, S. A. et al. Regression of fibrosis by cilostazol in a rat model of thioacetamide-induced liver fibrosis: Up regulation of hepatic cAMP, and modulation of inflammatory, oxidative stress and apoptotic biomarkers. PLoS One 14, e0216301. https:\/\/doi.org\/10.1371\/journal.pone.0216301 (2019).","journal-title":"PLoS One"},{"key":"45341_CR73","doi-asserted-by":"publisher","first-page":"7453","DOI":"10.1007\/s00210-024-03734-z","volume":"398","author":"PL Misar","year":"2025","unstructured":"Misar, P. L. & Otari, K. V. Investigation of the protective effect of cilostazol on acute lung injury-mediated inflammation and in silico molecular modelling studies of inflammatory signalling pathway: a repurposing study. Naunyn. Schmiedebergs Arch. Pharmacol. 398, 7453\u20137473. https:\/\/doi.org\/10.1007\/s00210-024-03734-z (2025).","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"45341_CR74","doi-asserted-by":"publisher","first-page":"108471","DOI":"10.1016\/j.toxicon.2025.108471","volume":"265","author":"FM Alzahrani","year":"2025","unstructured":"Alzahrani, F. M. et al. Pharmacotherapeutic potential of artemetin against amiodarone instigated sub-chronic hepatotoxicity via modulating TLR4\/HMGB1\/RAGE and NF-\u03baB signaling pathways: An in-vivo and in-silico approach. Toxicon 265, 108471. https:\/\/doi.org\/10.1016\/j.toxicon.2025.108471 (2025).","journal-title":"Toxicon"},{"key":"45341_CR75","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/jpp\/rgab115","volume":"73","author":"K Luhach","year":"2021","unstructured":"Luhach, K., Kulkarni, G. T., Singh, V. P. & Sharma, B. Cilostazol attenuated prenatal valproic acid-induced behavioural and biochemical deficits in a rat model of autism spectrum disorder. J. Pharm. Pharmacol. 73, 1460\u20131469. https:\/\/doi.org\/10.1093\/jpp\/rgab115 (2021).","journal-title":"J. Pharm. Pharmacol."},{"key":"45341_CR76","doi-asserted-by":"publisher","first-page":"118275","DOI":"10.1016\/j.biopha.2025.118275","volume":"189","author":"HW Chiu","year":"2025","unstructured":"Chiu, H. W., Shih, C. C., Huang, H. J., Huang, T. H. & Sung, L. C. Cilostazol attenuates vascular inflammation via the regulation of TICAM1\/IRF3 signaling pathway. Biomed. Pharmacother. 189, 118275. https:\/\/doi.org\/10.1016\/j.biopha.2025.118275 (2025).","journal-title":"Biomed. Pharmacother."},{"key":"45341_CR77","doi-asserted-by":"publisher","first-page":"12474","DOI":"10.1038\/s41598-022-16843-7","volume":"12","author":"N Ju","year":"2022","unstructured":"Ju, N. et al. Prevention of bleomycin-induced pulmonary fibrosis by a RANKL peptide in mice. Sci. Rep. 12, 12474. https:\/\/doi.org\/10.1038\/s41598-022-16843-7 (2022).","journal-title":"Sci. Rep."},{"key":"45341_CR78","doi-asserted-by":"publisher","first-page":"104368","DOI":"10.1016\/j.drudis.2025.104368","volume":"30","author":"SL Harding-Fox","year":"2025","unstructured":"Harding-Fox, S. L. & Cellek, S. The role of cyclic adenosine monophosphate (cAMP) in pathophysiology of fibrosis. Drug Discov. Today 30, 104368. https:\/\/doi.org\/10.1016\/j.drudis.2025.104368 (2025).","journal-title":"Drug Discov. Today"},{"key":"45341_CR79","doi-asserted-by":"publisher","first-page":"669227","DOI":"10.3389\/fphar.2021.669227","volume":"12","author":"MJ Roberts","year":"2021","unstructured":"Roberts, M. J. et al. Inhibition of the proliferation of human lung fibroblasts by prostacyclin receptor agonists is linked to a sustained cAMP signal in the nucleus. Front. Pharmacol. 12, 669227. https:\/\/doi.org\/10.3389\/fphar.2021.669227 (2021).","journal-title":"Front. Pharmacol."},{"key":"45341_CR80","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1080\/15376516.2020.1774829","volume":"30","author":"AM Abdel-Aziz","year":"2020","unstructured":"Abdel-Aziz, A. M., Mohamed, A. S. M., Abdelazem, O., Okasha, A. M. M. & Kamel, M. Y. Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1. Toxicol. Mech. Methods. 30, 526\u2013535. https:\/\/doi.org\/10.1080\/15376516.2020.1774829 (2020).","journal-title":"Toxicol. Mech. Methods"},{"key":"45341_CR81","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052593","author":"M Sohn","year":"2024","unstructured":"Sohn, M. & Lim, S. The role of cilostazol, a phosphodiesterase-3 inhibitor, in the development of atherosclerosis and vascular biology: A review with meta-analysis. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms25052593 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"45341_CR82","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02898-9","volume":"25","author":"X Ju","year":"2024","unstructured":"Ju, X. et al. Regulation of myofibroblast dedifferentiation in pulmonary fibrosis. Respir. Res. 25, 284. https:\/\/doi.org\/10.1186\/s12931-024-02898-9 (2024).","journal-title":"Respir. Res."},{"key":"45341_CR83","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1021\/pr060427q","volume":"6","author":"P Conrotto","year":"2007","unstructured":"Conrotto, P., Yakymovych, I., Yakymovych, M. & Souchelnytskyi, S. Interactome of transforming growth factor-beta type I receptor (TbetaRI): Inhibition of TGFbeta signaling by Epac1. J. Proteome Res. 6, 287\u2013297. https:\/\/doi.org\/10.1021\/pr060427q (2007).","journal-title":"J. Proteome Res."},{"key":"45341_CR84","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1658001","volume":"12","author":"W Li","year":"2025","unstructured":"Li, W., Xie, Y., Chen, Z., Cao, D. & Wang, Y. Epithelial-mesenchymal transition in pulmonary fibrosis: Molecular mechanisms and emerging therapeutic strategies. Front Med (Lausanne) 12, 1658001. https:\/\/doi.org\/10.3389\/fmed.2025.1658001 (2025).","journal-title":"Front Med (Lausanne)"},{"key":"45341_CR85","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.607483","volume":"8","author":"J Di Gregorio","year":"2020","unstructured":"Di Gregorio, J. et al. The epithelial-to-mesenchymal transition as a possible therapeutic target in fibrotic disorders. Front. Cell Dev. Biol. 8, 607483. https:\/\/doi.org\/10.3389\/fcell.2020.607483 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"45341_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118201","volume":"258","author":"S Mazumder","year":"2020","unstructured":"Mazumder, S., Barman, M., Bandyopadhyay, U. & Bindu, S. Sirtuins as endogenous regulators of lung fibrosis: A current perspective. Life Sci. 258, 118201. https:\/\/doi.org\/10.1016\/j.lfs.2020.118201 (2020).","journal-title":"Life Sci."},{"key":"45341_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.177194","volume":"987","author":"ES Gad","year":"2025","unstructured":"Gad, E. S. et al. Cilostazol counteracts mitochondrial dysfunction in hepatic encephalopathy rat model: Insights into the role of cAMP\/AMPK\/SIRT1\/PINK-1\/parkin hub and p-CREB\/BDNF\/TrkB neuroprotective trajectory. Eur. J. Pharmacol. 987, 177194. https:\/\/doi.org\/10.1016\/j.ejphar.2024.177194 (2025).","journal-title":"Eur. J. Pharmacol."},{"key":"45341_CR88","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1389454","volume":"16","author":"J Kong","year":"2024","unstructured":"Kong, J. et al. Oxidative stress in the brain-lung crosstalk: Cellular and molecular perspectives. Front. Aging Neurosci. 16, 1389454. https:\/\/doi.org\/10.3389\/fnagi.2024.1389454 (2024).","journal-title":"Front. Aging Neurosci."},{"key":"45341_CR89","doi-asserted-by":"crossref","unstructured":"Szychowski, K. A. Current State of Knowledge on Amiodarone (AMD)-Induced Reactive Oxygen Species (ROS) Production in In Vitro and In Vivo Models. 5, 16 (2025).","DOI":"10.3390\/oxygen5030016"},{"key":"45341_CR90","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2024.119676","volume":"1871","author":"A Mohanan","year":"2024","unstructured":"Mohanan, A., Washimkar, K. R. & Mugale, M. N. Unraveling the interplay between vital organelle stress and oxidative stress in idiopathic pulmonary fibrosis. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1871, 119676. https:\/\/doi.org\/10.1016\/j.bbamcr.2024.119676 (2024).","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"45341_CR91","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s00210-022-02233-3","volume":"395","author":"R de Oliveira Lopes","year":"2022","unstructured":"de Oliveira Lopes, R. et al. Cilostazol attenuates cardiac oxidative stress and inflammation in hypercholesterolemic rats. Naunyn Schmiedebergs Arch. Pharmacol. 395, 789\u2013801. https:\/\/doi.org\/10.1007\/s00210-022-02233-3 (2022).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"45341_CR92","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271591","volume":"17","author":"ZM Saeed","year":"2022","unstructured":"Saeed, Z. M., Khattab, M. I., Khorshid, N. E. & Salem, A. E. Ellagic acid and cilostazol ameliorate amikacin-induced nephrotoxicity in rats by downregulating oxidative stress, inflammation, and apoptosis. PLoS One 17, e0271591. https:\/\/doi.org\/10.1371\/journal.pone.0271591 (2022).","journal-title":"PLoS One"},{"key":"45341_CR93","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s43188-023-00217-w","volume":"40","author":"R Sun","year":"2024","unstructured":"Sun, R. et al. Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure. Toxicol. Res. 40, 189\u2013202. https:\/\/doi.org\/10.1007\/s43188-023-00217-w (2024).","journal-title":"Toxicol. Res."},{"key":"45341_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.114066","volume":"244","author":"Q Tang","year":"2022","unstructured":"Tang, Q. et al. Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2\/STAT3 signaling pathways. Ecotoxicol. Environ. Saf. 244, 114066. https:\/\/doi.org\/10.1016\/j.ecoenv.2022.114066 (2022).","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"45341_CR95","doi-asserted-by":"publisher","first-page":"8662","DOI":"10.1111\/jcmm.16821","volume":"25","author":"H Ying","year":"2021","unstructured":"Ying, H. et al. Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-\u03b21\/Smad3 pathway. J. Cell. Mol. Med. 25, 8662\u20138675. https:\/\/doi.org\/10.1111\/jcmm.16821 (2021).","journal-title":"J. Cell. Mol. Med."},{"key":"45341_CR96","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.3892\/etm.2018.6378","volume":"16","author":"X Song","year":"2018","unstructured":"Song, X., Yu, W. & Guo, F. Pirfenidone suppresses bleomycin-induced pulmonary fibrosis and periostin expression in rats. Exp. Ther. Med. 16, 1800\u20131806. https:\/\/doi.org\/10.3892\/etm.2018.6378 (2018).","journal-title":"Exp. Ther. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45341-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45341-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45341-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:57:54Z","timestamp":1778684274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45341-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":96,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45341"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45341-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"2 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study protocol was approved by the Research Ethics Committee , Horus University-Egypt, New Damietta, Egypt\u00a0(Ethical code: PH-2025-005).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15055"}}