{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:25:59Z","timestamp":1789424759009,"version":"build-2803163510"},"reference-count":52,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>To investigate whether obstructing the cysteinyl leukotriene receptor-1 (CYSLTR1) with zafirlukast diminishes experimentally induced gastric ulcer (GU) in rats by modulating inflammation and apoptosis. Gastric ulcers affect approximately 10% of the global population and can lead to serious complications such as gastrointestinal perforation and bleeding. Leukotrienes are proinflammatory compounds, and cysteinyl leukotrienes, such as LTC4, LTD4, and LTE4, that are potent proinflammatory mediators. Rats were orally administered a single oral dose of 80\u2009mg\/kg of indomethacin to induce GU. The rats were administered an oral dose of 20\u2009mg\/kg Zafirlukast. Gastric tissues were collected for macrostructural and microstructural analyses. A portion of gastric tissue was used to assess the genetic expression and protein levels of CYSLTR1, NF\u03baB, TNF-\u03b1, IL-1\u03b2\/4\/10, JNK, PKB, and caspase-3. The gastric sections were subjected to hematoxylin\/eosin and Masson trichrome staining and immunohistochemical staining with anti-TNF-\u03b1 and anti-caspase-3 antibodies. Zafirlukast blocked the expression of CYSLTR1. Analysis of micro-images of GU rats revealed damage to surface cells and glandular epithelial cells caused by inflammatory cell infiltration, which was mitigated by Zafirlukast. Additionally, Zafirlukast treatment significantly reduced NF\u03baB, TNF-\u03b1, IL-1\u03b2, JNK, PKB, and caspase-3 while increasing IL-4 and IL-10. Zafirlukast successfully reduced experimentally induced gastric ulcers in rats. Its mechanism of action includes inhibition of CYSLTR1, diminishing the inflammatory pathway. This is demonstrated by a decrease in the levels of NF\u03baB, TNF-\u03b1, and IL-1\u03b2, along with an increase in the levels of IL-4 and IL-10. Additionally, Zafirlukast exerted anti-apoptotic effects by downregulating the expression of JNK, PKB, and caspase-3.<\/jats:p>","DOI":"10.1177\/03946320251351083","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T08:43:46Z","timestamp":1750495426000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Blocking leukotriene receptors improve experimentally induced gastric ulcers in rats by inhibiting inflammation and apoptosis"],"prefix":"10.1177","volume":"39","author":[{"given":"Hanan M.","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-4881","authenticated-orcid":false,"given":"Alaa","family":"Bagalagel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Diri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Noor","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deina","family":"Almasri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douha F.","family":"Bannan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-0742","authenticated-orcid":false,"given":"Mohammed Z.","family":"Nasrullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-3919","authenticated-orcid":false,"given":"Mohammed M. 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