{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:26:15Z","timestamp":1785216375028,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver injury caused by acetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. The mode of APAP\u2010induced cell death has been controversially discussed with ferroptosis emerging as a more recent hypothesis. Ferroptosis is characterized by ferrous iron\u2010catalyzed lipid peroxidation (LPO) causing cell death, which can be prevented by the lipophilic antioxidants ferrostatin\u20101 and UAMC\u20103203. To assess the efficacy of these ferroptosis inhibitors, we used two murine models of APAP hepatotoxicity, APAP overdose alone or in combination with FeSO<jats:sub>4<\/jats:sub> in fasted male C57BL\/6J mice. APAP triggered severe liver injury in the absence of LPO measured as hepatic malondialdehyde (MDA) levels. In contrast, ferrous iron co\u2010treatment aggravated APAP\u2010induced liver injury and caused extensive LPO. Standard doses of ferrostatin\u20101 did not affect MDA levels or the injury in both models. In contrast, UAMC\u20103203 partially protected in both models and reduced LPO in the presence of ferrous iron. However, UAMC\u20103203 attenuated the translocation of phospho\u2010JNK through downregulation of the mitochondrial anchor protein Sab resulting in reduced mitochondrial dysfunction and liver injury. Thus, APAP toxicity does not involve ferroptosis under normal conditions. The lack of effects of ferroptosis inhibitors in the pathophysiology indicates that ferroptosis signaling pathways are not relevant therapeutic targets.<\/jats:p>","DOI":"10.1002\/jbt.23791","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T10:40:05Z","timestamp":1722422405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of ferroptosis inhibitors in a murine model of acetaminophen\u2010induced liver injury"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-0164","authenticated-orcid":false,"given":"Olamide B.","family":"Adelusi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9532-8229","authenticated-orcid":false,"given":"Yasaman","family":"Etemadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-1164","authenticated-orcid":false,"given":"Jephte Y.","family":"Akakpo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-2409","authenticated-orcid":false,"given":"Anup","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-6980","authenticated-orcid":false,"given":"Hartmut","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000458"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.24347"},{"key":"e_1_2_10_5_1","first-page":"211","volume":"187","author":"Mitchell J. 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