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Therefore, we evaluated the efficacy of febuxostat (FBX), a specific inhibitor of xanthine oxidase and antioxidant, in blocking hepatotoxicity associated with DOX in rats. Rats were treated with FBX (10 or 15\u00a0mg\/kg\/day orally for 2\u00a0weeks) and given DOX (15\u00a0mg\/kg as single dose at the 7th day, intraperitoneal) to induce hepatotoxicity. The results indicated that FBX could reduce the pathological alterations of liver tissues induced by DOX and ameliorate the inappropriate changes in liver function biomarkers (AST, ALT, and ALP) in serum, oxidative stress parameters (catalase, superoxide dismutase, NOX1, NQO-1, HO-1, Keap-1, and Nrf2) and inflammatory markers in the liver (NF-\u03baB p65, TNF-\u03b1, NLRP3). Additionally, FBX attenuated the p53, BAX, cytochrome C, caspase-9, and caspase-3 levels to restrain cell apoptosis. In addition, FBX therapy was found to increase protein levels of SIRT-1 and AMPK in the liver. These findings demonstrate that FBX can reduce the hepatotoxicity caused by DOX in rats through mechanisms that counteract oxidative stress, inflammation, and apoptosis.<\/jats:p>","DOI":"10.1007\/s00210-025-03808-6","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T04:32:49Z","timestamp":1739507569000},"page":"10125-10137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Febuxostat protects from Doxorubicin induced hepatotoxicity in rats via regulation of NF-\u03baB p65\/NLRP3 inflammasome and SIRT-1\/AMPK pathways"],"prefix":"10.1007","volume":"398","author":[{"given":"Ahmed M.","family":"El-Dessouki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman H.","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed A.","family":"Raslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa I.","family":"Alwakeel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany A.","family":"Alzokaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"3808_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115794","volume":"216","author":"BA Abdel-Wahab","year":"2023","unstructured":"Abdel-Wahab BA, El-Shoura EA, Habeeb MS, Zafaar D (2023) Febuxostat alleviates Arsenic Trioxide-Induced renal injury in rats: insights on the crosstalk between NLRP3\/TLR4, Sirt-1\/NF-\u03baB\/TGF-\u03b2 signaling pathways, and miR-23b-3p, miR-181a-5b expression. 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