{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:38:06Z","timestamp":1787017086174,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Anthracyclines remain among the most effective cytotoxic drugs, but their cumulative cardiotoxicity limits dosing and threatens survivors with heart failure. The discovery that doxorubicin kills cardiomyocytes substantially through ferroptosis\u2014an iron\u2010dependent, lipid\u2010peroxidation\u2010driven cell death\u2014has reframed the mechanism and identified a defined target, and the field has rapidly populated with iron chelators, radical\u2010trapping inhibitors and Nrf2\/GPX4\u2010activating natural products reported to protect the heart. This review argues that the prevailing enthusiasm is mismatched to the biology in two respects. First, doxorubicin engages several regulated cell\u2010death programmes at once, and ferroptosis operates within a multilayered defence network (GPX4, the FSP1\u2013coenzyme\u2010Q10 axis, mitochondrial DHODH and GTP\u2010cyclohydrolase\u20101\/tetrahydrobiopterin); blocking one node redistributes death and helps explain why ferroptosis inhibitors have failed, and even worsened outcomes, in some doxorubicin models. Second, and more fundamentally, ferroptosis is tumour\u2010suppressive and contributes to the anticancer efficacy of chemotherapy, radiotherapy and immunotherapy, so systemic ferroptosis inhibition to protect the heart risks shielding the tumour\u2014a paradox the cardioprotection literature largely ignores. The single approved agent, dexrazoxane, is acceptable precisely because evidence indicates it spares antitumour efficacy. The path to translatable cardioprotection therefore runs not through broad ferroptosis blockade but through cardiac\u2010 and mitochondria\u2010selective, appropriately timed reinforcement of iron handling and lipid\u2010peroxidation defence, validated against hard cardiac endpoints and preserved tumour control. Ferroptosis is a genuine and central mechanism of anthracycline cardiotoxicity; converting that mechanism into safe therapy is a harder problem than the current literature acknowledges.<\/jats:p>","DOI":"10.1002\/jat.70402","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:10:42Z","timestamp":1787015442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferroptosis in Anthracycline Cardiotoxicity: Mechanisms, the Cardioprotection Paradox and the Limits of Single\u2010Pathway Thinking"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-0151","authenticated-orcid":false,"given":"Rony Abdi","family":"Syahputra","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abn8017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/619185"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1139\/y11-020","article-title":"Amelioration of Doxorubicin\u2010Induced Cardiotoxicity by Deferiprone in Rats","volume":"89","author":"Ammar E. 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