{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:06:08Z","timestamp":1791414368241,"version":"4.3.3"},"reference-count":60,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Benign prostatic hyperplasia (BPH) is a prevalent condition among aging males, significantly impacting their quality of life. Emerging evidence links elevated uric acid (UA) levels to prostatic inflammation and hyperplasia, potentially through oxidative stress and activation of proliferative pathways. However, the role of UA in BPH pathogenesis remains poorly defined. The study aims to investigate the potential protective effects of a natural phenolic compound, eugenol, and\/or probenecid against testosterone\u2010BPH in rats, along with the possible underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BPH was induced by administering testosterone (3\u2009mg\/kg; s.c.) for 2 weeks, either alone or following a 1\u2010week pretreatment with probenecid (200\u2009mg\/kg\/day; i.p.), eugenol (10\u2009mg\/kg\/day; p.o.), or their combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results demonstrated a significant increase in prostate index, cell survival markers such as cyclin D1 expression, and histopathological features indicative of BPH following testosterone administration. Furthermore, testosterone led to elevated uric acid levels, oxidative stress, inflammatory markers, and activation of pro\u2010survival pathways including PI3\u2010K\/Akt\/mTOR and NF\u03baB. However, treatment with probenecid, eugenol, or their combination effectively attenuated these alterations, demonstrating their anti\u2010inflammatory, antioxidative, and anti\u2010hyperproliferative effects. Notably, combination therapy exhibited superior efficacy compared to individual treatments. These findings suggest that probenecid and eugenol may mitigate testosterone\u2010induced BPH by targeting the uric acid\u2010induced inflammation and pro\u2010survival pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides novel insights into the therapeutic potential of probenecid and eugenol as adjunctive treatments for BPH, offering promising avenues for further clinical investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.70026","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:31:36Z","timestamp":1754026296000},"page":"1412-1423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Probenecid and Eugenol Mitigate Testosterone Induced Benign Prostatic Hyperplasia by Targeting Uric Acid\u2010Induced Inflammation and Pro\u2010Survival Pathways"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5240-2949","authenticated-orcid":false,"given":"Nibrass Taher","family":"Abdali","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy Al\u2010Farahidi University Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin S.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala F.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila A. 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