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This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)\u2010induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel\u2010administered control group received intraperitoneal injection of paclitaxel at a dose of 2\u2009mg\/Kg body weight twice a week for 6 weeks. Treated paclitaxel\u2010administered groups were given paclitaxel similar to the paclitaxel\u2010administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10\u2009mg\/Kg body weight every other day for 6 weeks. The treatment of paclitaxel\u2010administered rats with rutin and hesperidin significantly reduced paclitaxel\u2010induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma\u2010glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel\u2010induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase\u20103) and pro\u2010inflammatory cytokine (tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic>) expressions were decreased by the three treatments in paclitaxel\u2010administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel\u2010administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.<\/jats:p>","DOI":"10.1155\/2023\/2738351","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T02:35:05Z","timestamp":1685154905000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats <i>via<\/i> Their Antioxidant, Anti\u2010Inflammatory, and Antiapoptotic Activities"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6474-3370","authenticated-orcid":false,"given":"Yasmine A.","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8036-0839","authenticated-orcid":false,"given":"Hanan A.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-2411","authenticated-orcid":false,"given":"Mohamed","family":"Abdel-Gabbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-0933","authenticated-orcid":false,"given":"Noha A.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1854-2679","authenticated-orcid":false,"given":"Kandil A. 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