{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:15:15Z","timestamp":1790079315502,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Drug\u2010induced hepatic insult is the most frequent antecedent of liver dysfunction. The folic acid antagonist, Methotrexate (MTRX), has tremendous applications in the treatment of various tumors, autoimmune disorders, and inflammatory diseases, but hepatotoxicity limits its clinical use. This study aimed to investigate the role of AGM against MTRX\u2010induced hepatotoxicity and its possible underlying mechanistic pathways. Mice were pre\u2010treated with AGM (14\u2009mg\/kg, orally) and administered a single injection of MTRX (20\u2009mg\/kg, i.p.) on Day 6. MTRX\u2010induced hepatic injury was evidenced by marked increase in serum hepatotoxicity markers, decreased hepatic reduced glutathione (GSH) level and superoxide dismutase (SOD) activity, and hepatic interleukin (IL)\u221210 content, besides increased levels of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), IL\u20106, c\u2010Jun N\u2010terminal kinase (JNK), BCL2\u2010associated X protein (BAX), and Caspase\u20103. Moreover, MTRX increased hepatic expression of nuclear factor kappa\u2010B (NF\u2010\u03baB), and inducible nitric oxide synthase (iNOS), AGM pretreated group revealed a substantial elevation in hepatic antioxidant markers, besides marked reduction in the serum levels of hepatotoxicity markers and hepatic content of MDA, NO, NF\u2010\u03baB, TNF\u2010\u03b1, IL\u20106, iNOS, JNK, BAX, and Caspase\u20103. Furthermore, the protective effect of AGM was affirmed by liver histological examination. Therefore, AGM attenuates MTRX's liver injury by mitigating oxidative stress, inflammation, and apoptosis. These findings suggest that AGM could be considered as a potential adjuvant in MTRX\u2010induced toxicity.<\/jats:p>","DOI":"10.1002\/jbt.71009","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:50:54Z","timestamp":1783320654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agmatine Attenuates Methotrexate\u2010Induced Hepatotoxicity: Targeting Oxidative Stress, Inflammation, and Apoptotic Pathways"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0669-4480","authenticated-orcid":false,"given":"Haitham M.","family":"Sewilam","sequence":"first","affiliation":[{"name":"Department of Histology, Faculty of Medicine Capital University (formerly Helwan University)  Cairo Egypt"},{"name":"Department of Histology and Cell Biology, General Medicine Practice Program Batterjee Medical College  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-5533","authenticated-orcid":false,"given":"Dalia H.","family":"El\u2010Kashef","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-2901","authenticated-orcid":false,"given":"Hadeer M.","family":"Abouelezz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"issue":"9","key":"e_1_2_11_2_1","article-title":"Overview of Methotrexate Toxicity: A Comprehensive Literature Review","volume":"14","author":"Hamed K. 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