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Twenty-four male rats were divided into four groups: sham control, testicular IR, and two RVX treatment groups (7 and 14\u00a0mg\/kg) administered for one week prior to IR. Testicular IR led to significant impairment in testicular function, evidenced by an 86.5% reduction in testosterone levels and marked oxidative stress with an 189.3% increase in malondialdehyde (MDA). IR injury also triggered substantial elevations in apoptotic markers (271% increase in Bax (Bcl2-associated X protein) and 65.9% decrease in BCL2 (B-cell lymphoma 2), and inflammatory mediators (285.7% increase in NF\u03baB (nuclear factor-kappa B). Additionally, angiogenic markers showed dramatic increases, with VEGF (vascular endothelial growth factor) and HIF-1 (Hypoxia inducible factor-1) rising by 431.8% and 519%, respectively. RVX treatment demonstrated dose-dependent protective effects, with the 14\u00a0mg\/kg dose showing superior outcomes compared to 7\u00a0mg\/kg. The higher dose significantly improved hormonal function (486.8% increase in testosterone), reduced oxidative stress (51.8% reduction in MDA), modulated apoptotic markers (68.3% decrease in BAX, 159.1% increase in BCL2), and normalized angiogenic factors (71.8% reduction in HIF-1). In conclusion, RVX demonstrated significant therapeutic potential in protecting against testicular IR injury, with the 14\u00a0mg\/kg dose showing optimal protective effects. Reduction in HIF-1\u03b1 and VEGF protein expression mediated RVX\u2019s anti-oxidant, anti-inflammatory, and anti-apoptotic effect in rats subjected to testicular IR.<\/jats:p>","DOI":"10.1038\/s41598-025-10395-2","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T21:13:22Z","timestamp":1753823602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Involvement of hypoxia-inducible factor1-alpha in the protective effect of rivaroxaban against testicular ischemia-reperfusion in rats"],"prefix":"10.1038","volume":"15","author":[{"given":"Marwan Abdel","family":"Baset","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"El Awdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa S.","family":"Khattab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma A.","family":"El-Marasy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"10395_CR1","unstructured":"Tullington, J. 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