{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:17:11Z","timestamp":1793297831179,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1477600"],"award-info":[{"award-number":["23ZR1477600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tamoxifen is an inhibitor of estrogen receptors and was originally developed for breast cancer therapy. Besides, tamoxifen is widely used for Cre\u2010estrogen receptor\u2010mediated conditional knockout in transgenic mice. However, we found that the 3\u2010month feeding of 0.5\u2009g\/kg tamoxifen diet dramatically lowered the body weight of mice. The liver fat content and the serum lipid indicators were all decreased. But the liver injuries were identified, as illustrated by liver\/body ratio and serum ALT and AST levels. The Sirius red staining and \u03b1\u2010SMA staining even showed fibrosis in the liver. The increased lipid peroxidation indicators MDA and LPO, and ferroptosis markers COX\u20102, GPX4, SLC7A11, and ACSL4 implied the tamoxifen\u2010induced ferroptosis in the liver. We further found that tamoxifen induced hepatic iron deposition. The investigation of iron transporters found that tamoxifen upregulated ferric iron reductase STEAP3, ferrous iron transporter DMT1, and iron storage molecule ferritin, which were probably the reasons for tamoxifen\u2010induced iron deposition. The downregulation of the transferrin receptor and upregulation of hepcidin were more likely the responses to iron deposition. In conclusion, we found that tamoxifen disturbed the iron metabolism and induced liver injuries and ferroptosis, warranting attention to the applications of tamoxifen in cancer therapy and conditional gene knockout.<\/jats:p>","DOI":"10.1096\/fj.202402553rr","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T10:24:37Z","timestamp":1736504677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prolonged tamoxifen treatment induces iron deposition and ferroptosis in the liver"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-939X","authenticated-orcid":false,"given":"Jianxin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nutrition Second Military Medical University  Shanghai 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