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Thus, searching for a hepatoprotective agent is highly required to prevent the accompanied hepatic hazards. The current study aimed to investigate the potential benefit and mechanisms of action of rupatadine (RU), a Platelet-activating factor (PAF) antagonist, in the prevention of 5-FU-related hepatotoxicity in rats. Hepatotoxicity was developed in male albino rats by a single 5-FU (150\u00a0mg\/kg) intra-peritoneal injection\u00a0on the 7th day of the experiment. RU (3\u00a0mg\/kg\/day) was orally administrated to the rodents for 10\u00a0days. Hepatic toxicity was assessed by measuring both liver and body weights, serum\u00a0alanine aminotransferase and aspartate aminotransferase\u00a0(ALT and AST), hepatic oxidative stress parameters (malondialdehyde (MDA), nitric oxide levels (NOx), reduced glutathione (GSH), superoxide dismutase (SOD)), and heme oxygenase-1 (HO-1). Inflammatory markers expressions (inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF\u03b1), interleukins; IL-1B, IL-6), the apoptotic marker (caspase-3), and PAF were measured in the hepatic tissue. 5-FU-induced hepatotoxicity was proved by the biochemical along with histopathological assessments. RU\u00a0ameliorated 5-FU-induced liver damage as proved by the improved serum ALT, AST, and hepatic oxidative stress parameters, the attenuated expression of hepatic pro-inflammatory cytokines and PAF, and the up-regulation of HO-1. Therefore, it can be concluded that RU pretreatment exerted a hepatoprotective effect against 5-FU-induced liver damage through both its powerful anti-inflammatory, antioxidant, and anti-apoptotic effect.<\/jats:p>","DOI":"10.1007\/s11356-022-18899-4","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T16:30:44Z","timestamp":1643992244000},"page":"40190-40203","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of Platelet-activating factor and HO-1 in mediating the protective effect of rupatadine against 5-fluorouracil-induced hepatotoxicity in rats"],"prefix":"10.1007","volume":"29","author":[{"given":"Hanaa Mohamed","family":"Khalaf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Mohamed Naguib Abdel","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam Mohamed","family":"Abdalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermeen N.","family":"Welson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa Yehia","family":"Abdelzaher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Alzhraa Fouad","family":"Abdelbaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"issue":"2","key":"18899_CR1","doi-asserted-by":"publisher","first-page":"e13472","DOI":"10.1111\/and.13472","volume":"52","author":"AM Abdel-Aziz","year":"2019","unstructured":"Abdel-Aziz AM, Hafez SM (2019) Sitagliptin protects male albino rats with testicular ischaemia\/reperfusion damage: Modulation of VCAM-1 and VEGF-A. 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