{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T14:38:14Z","timestamp":1782225494935,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p><jats:bold>Valproic acid<\/jats:bold> (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon\u2010like peptide 1 receptor (GLP\u20101R) agonist that act as a novel antidiabetic drug with broad\u2010spectrum anti\u2010inflammatory and antioxidant effects. <jats:bold>This study tested<\/jats:bold> the protective effect of liraglutide against VPA\u2010induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid\u2010treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid &amp; liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT\u2010PCR technique. Hepatic NF\u2010\u03baB and TNF\u2010\u03b1 were detected immunohistochemically. <jats:bold>Results proved<\/jats:bold> that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA\u2010hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA\u2010induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3855","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T01:40:02Z","timestamp":1695951602000},"page":"1209-1219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1\/RAGE axis and RIPK3\/MLKL mediated necroptosis"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-4719","authenticated-orcid":false,"given":"Marwa Mohamed","family":"Atef","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine, Tanta University  Tanta 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