{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:02Z","timestamp":1792788602604,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Doxorubicin (DOX) is a member of the anthracycline class that acts as a chemotherapeutic drug. It causes toxicity by killing both noncancerous cells and cancer cells, even in organs that are not its intended target. Hepatotoxicity from DOX injection is mainly induced by the liver's involvement in the detoxifying process. Exposure to DOX mainly causes inflammatory insult, oxidative stress (OS), and apoptotic cell death, which cause hepatic damage. To lessen the hepatotoxicity caused by DOX, it is essential to comprehend these processes and investigate protective medications. Thus, our goal was to investigate the molecular pathways responsible for DOX\u2010induced hepatotoxicity, focusing on Sirt\u20101\/Nrf2, NF\u03ba\u2010B, and P53. Additionally, our work is designed to assess the potential of Hesperidin to confer protection against liver injury, which is administered orally in two different doses, to estimate the most efficient dose. In vivo investigations were performed on adult male rats arbitrarily allocated to five groups, including a normal control group, Hesperidin 100\u2009mg\/kg treated group, DOX exposure, and DOX exposure treated with Hesperidin (50, 100\u2009mg\/kg), respectively. Increased MDA and MPO levels and SIRT\u20101 suppression were indicators of hepatic OS brought on by DOX exposure, which also disrupted antioxidant pathways and triggered inflammatory and apoptotic pathways. Additionally, the elevated liver function biomarkers and observed histological alterations confirmed these results. Both doses effectively modified these effects, with the high dose, 100\u2009mg\/kg, revealing superior effectiveness in alleviating Dox\u2010induced biochemical and histological changes. The present research sheds information on the molecular processes that accompany liver damage caused by DOX while also highlighting Hesperidin's hepatoprotective capabilities. These data imply that Hesperidin, especially when administered at 100\u2009mg\/kg, has a powerful effect as a therapeutic compound for combating DOX\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jbt.70465","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T05:59:37Z","timestamp":1756447177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hesperidin Reduces Hepatic Injury Induced by Doxorubicin in Rat Model Through Its Antioxidative and Anti\u2010Inflammatory Effects, Focusing on SIRT\u20101\/NRF\u20102 Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1835-5806","authenticated-orcid":false,"given":"Alzahraa A.","family":"Elhemiely","sequence":"first","affiliation":[{"name":"Department of Pharmacology Egyptian Drug Authority (EDA)\u2014Formerly NODCAR Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa H.","family":"El\u2010Fayoumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Heliopolis University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-9480","authenticated-orcid":false,"given":"Mohamed H. 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