{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:28:04Z","timestamp":1788492484463,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University","award":["PNURSP2024R227"],"award-info":[{"award-number":["PNURSP2024R227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Doxorubicin (DOX), an anticancer drug, is used to treat several types of tumors, but it has detrimental side effects that restrict its therapeutic efficacy. One is the iron-dependent form of ferroptosis, which is characterized by elevated ROS production and iron overload. Syzygium aromaticum has a diverse range of biological and pharmaceutical actions due to their antioxidant properties. This study investigated the effect of S. aromaticum extract (SAE) on hepatotoxicity caused by DOX in rats. Phytochemical analysis was performed to assess compounds in SAE. The ADMETlab 2.0 web server was used to predict the pharmacokinetic properties of the most active components of SAE when DOX was injected into rats. Molecular docking studies were performed using AutoDock Vina. Forty male Sprague Dawley rats were divided into four groups of ten rats each (G1 was a negative control group, G2 was given 1\/10 of SAE LD50 by oral gavage (340 mg\/kg), G3 was given 4 mg\/kg of DOX intraperitoneally (i.p.) once a week for a month, and G4 was administered DOX as in G3 and SAE as in G2). After a month, biochemical and histopathological investigations were performed. Rats given SAE had promising levels of phytochemicals, which could significantly ameliorate DOX-induced hepatotoxicity by restoring biochemical alterations, mitigating ferroptosis, and upregulating the NRF-2\u2013SLC7A-11\u2013GPX-4 signaling pathway. These findings suggest that SAE could potentially alleviate DOX-induced hepatotoxicity in rats.<\/jats:p>","DOI":"10.3390\/ijms252312541","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T06:41:48Z","timestamp":1732257708000},"page":"12541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Syzygium aromaticum Extract Mitigates Doxorubicin-Induced Hepatotoxicity in Male Rats"],"prefix":"10.3390","volume":"25","author":[{"given":"Alaa Muqbil","family":"Alsirhani","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal S.","family":"Abu-Almakarem","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al Baha 65431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha Abdullah","family":"Alwaili","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwa","family":"Aljohani","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Taibah University, Yanbu Branch, Yanbu 46423, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5989-8308","authenticated-orcid":false,"given":"Ibtisam","family":"Alali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljazi Abdullah","family":"AlRashidi","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, University of Ha\u2019il, Ha\u2019il 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najlaa Yousef","family":"Abuzinadah","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Science, University of Jeddah, Jeddah 23714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Abdulrahman","family":"Alkhodair","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-0387","authenticated-orcid":false,"given":"Maysa A.","family":"Mobasher","sequence":"additional","affiliation":[{"name":"Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahiyat","family":"Alothaim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-8202","authenticated-orcid":false,"given":"Thamir M.","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1511-6033","authenticated-orcid":false,"given":"Karim Samy","family":"El-Said","sequence":"additional","affiliation":[{"name":"Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.biopha.2018.02.055","article-title":"Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it","volume":"100","author":"Li","year":"2018","journal-title":"Biomed. 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