{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:06:55Z","timestamp":1793318815734,"version":"4.5.0"},"reference-count":210,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Methotrexate (MTX) is an antimetabolite drug utilized for managing a variety of cancers and autoinflammatory conditions. MTX may trigger detrimental effects in mout, h tissues, including salivary gland impairment. Bosentan (BOS), a drug that blocks endothelin receptors, has strengthened antioxidant, anti-inflammatory, and anti-apoptotic properties. The study aimed to estimate the protective effect of BOS on MTX-exacerbated salivary changes in Wistar Albino rats. Thirty male rats were arbitrarily sorted into three groups of ten animals each. The control group received a normal saline for 18\u00a0days. The MTX (induction) group received MTX (25\u00a0mg\/kg) intraperitoneally on the 7th day of the experiment once daily for 6 consecutive days. The MTX\u2009+\u2009BOS group received BOS (50\u00a0mg\/kg) orally once a day for 18\u00a0days: 6\u00a0days before induction, 6\u00a0days 2-h after induction, and 6\u00a0days post-induction. Animals were euthanized on day 19, and salivary gland tissues were dissected for biochemical, histopathological, and immunohistochemical analyses. BOS dramatically improved MTX-aggravated biochemical and histopathological abnormalities, as evidenced by diminished Bax, caspase 3, TNF-\u03b1, IL-1\u03b2, MDA, and MPO levels, increased SOD, GSH, and GPX levels, and reduced degenerative changes in the granular convolute tubule, mucous acini, and striate duct. BOS further substantially upregulated MTX-induced decline of the Ki-67 and Bcl-2, as indicated by immunohistochemistry scoring methods. The anti-oxidative, ant-inflammatory, and antiapoptotic properties of BOS are a promising strategy for ameliorating the toxic effect of MTX on submandibular glandular tissues.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf007","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T12:18:15Z","timestamp":1736338695000},"source":"Crossref","is-referenced-by-count":30,"title":["The Possible effect of Bosentan on the methotrexate-induced salivary gland changes in male rats: histological and Immunohistochemical study"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-4903","authenticated-orcid":false,"given":"Rana Khairi","family":"Attarbashee","sequence":"first","affiliation":[{"name":"Department of Dental Basic Sciences, College of Dentistry, University of Mosul , Majmoaa Thqafiya St., Mosul 41002, +964 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