{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:48:18Z","timestamp":1782067698667,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"October University for Modern Sciences & Arts"},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While nephrotoxicity remains the most recognized adverse effect of cisplatin, hepatotoxicity is increasingly acknowledged as a significant clinical concern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study evaluated the hepatoprotective effect of dapagliflozin (DAPA), a selective sodium\u2013glucose cotransporter-2 inhibitor, focusing on its modulation of the PI3K\/Akt\u2013Nrf2\/HO-1 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar albino rats received oral dapagliflozin (5 or 10\u00a0mg\/kg\/day) for 14\u00a0days, with a single intraperitoneal injection of cisplatin (7.5\u00a0mg\/kg) administered on Day 7. Biochemical, molecular, and histopathological assessments were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cisplatin induced marked hepatic injury, evidenced by body weight loss, hepatomegaly, hyperglycemia, impaired liver function, oxidative stress, inflammation, and apoptosis dysregulation. Dapagliflozin pretreatment significantly and dose-dependently mitigated these effects. It reduced lipid peroxidation and nitric oxide levels while enhancing antioxidant defenses, including Nrf2, heme oxygenase-1, and superoxide dismutase. Additionally, dapagliflozin restored PI3K\/Akt signaling, suppressed NF-\u03baB-mediated inflammatory responses, and normalized apoptotic balance. Histological findings corroborated biochemical results, showing preservation of hepatic architecture, particularly at the higher dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dapagliflozin exerts significant hepatoprotective effects against cisplatin-induced toxicity via antioxidant, anti-inflammatory, and cytoprotective mechanisms, supporting its potential as an adjunct to improve cisplatin safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag066","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:51:16Z","timestamp":1780055476000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic evidence for PI3K\/Akt-driven reactivation of Nrf2\/HO-1 by dapagliflozin in acute cisplatin hepatotoxicity"],"prefix":"10.1093","volume":"78","author":[{"given":"Doaa Abou","family":"El-ezz","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Sciences & Arts (MSA University) , 6th of October City, Giza 12556 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha E","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre , Dokki, Cairo 12622 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan Khaled","family":"Fouad","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, October University for Modern Sciences & Arts (MSA University) , 6th of October City, Giza 12556 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan A","family":"Abd El-Baset","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Medical Research 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