{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T07:23:52Z","timestamp":1763191432305,"version":"3.45.0"},"reference-count":63,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Idiopathic pulmonary fibrosis is considered the most common type of interstitial lung disease. The principal aim of our research was to investigate the potential role of pazopanib treatment in alleviating bleomycin\u2010elicited pulmonary fibrosis and elucidate the underlying molecular mechanisms. Twenty\u2010four male mice were allocated into four groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096): control animals (received saline intraperitoneally (i.p.)), bleomycin group received bleomycin (40 U\/kg, i.p.) on 5 days, 0, 3, 7, 10, and 14, and bleomycin and pazopanib\u2010treated group received bleomycin on the specified days and then received pazopanib (10\u2009mg\/kg, i.p.) once daily starting on Day 15 to Day 28, plus pazopanib\u2010treated group, which received pazopanib only in the previously specified dose and duration. Our results demonstrated the promising role of pazopanib in mitigating pulmonary fibrosis, as reflected by the remarkable improvement in body weight loss and pulmonary histopathological features. This finding was primarily ascribed to the documented suppression of mitogen\u2010activated protein kinase kinase kinase 2 (MEKK2) and MEKK3 mRNA expressions, which subsequently repressed p\u2010c\u2010Jun N\u2010terminal kinase (p\u2010JNK1\/2) and p\u2010P38 group of protein kinases (p\u2010P38) protein expressions. Moreover, pazopanib administration to bleomycin\u2010treated mice remarkably adjusted the bleomycin\u2010mediated dysregulation of the levels of examined cytokines, including interleukin (IL)\u20101\u03b2, IL\u201013, IL\u201033, tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), and nuclear factor kappa\u2010B (NF\u2010\u03baB) P65. Remarkably, pazopanib treatment reversed the bleomycin\u2010induced elevation in transforming growth factor\u2010beta\u20101 (TGF\u2010\u03b21) and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) levels. Our research highlighted the beneficial role of pazopanib in attenuating bleomycin\u2010elicited lung fibrosis through the suppression of MEKK2 and MEKK3 and the modulation of JNK and P38 cascades.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70105","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T06:50:08Z","timestamp":1759128608000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting JNK1\/2 and P38 Mitogen\u2010Activated Protein Kinases With Pazopanib Mitigates Bleomycin\u2010Induced Lung Fibrosis"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-8525","authenticated-orcid":false,"given":"Rasha","family":"Abdelhady","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Fayoum University Fayoum Egypt"},{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy and Drug Technology, Egyptian Chinese University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-3658","authenticated-orcid":false,"given":"Rabab H.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Cairo University Cairo Egypt"},{"name":"School of Pharmacy Newgiza University Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4309-7095","authenticated-orcid":false,"given":"Nancy S.","family":"Younis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Faculty of Clinical Pharmacy, King Faisal University Al Hofuf Saudi Arabia"},{"name":"Zagazig University Hospitals Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-1035","authenticated-orcid":false,"given":"Omaima","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Sinai University\u2010Kantara Branch Ismailia Egypt"},{"name":"General Division for Biological Control and Research Egyptian Drug Authority Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai Abdallah","family":"Elhemely","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Beni\u2010suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0499","authenticated-orcid":false,"given":"Ahmed M.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Umm Al Qura University Makkah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuruq E.","family":"Alsufyani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Taif University Taif Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-6901","authenticated-orcid":false,"given":"Hany H.","family":"Arab","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Taif University Taif Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed S.","family":"Abdel\u2010Hamid","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy, Fayoum University Fayoum 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