{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:28:15Z","timestamp":1790116095320,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"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":["Liver International"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Hepatotoxicity is a well\u2010defined reaction to methotrexate (MTX), a drug commonly used for the treatment of rheumatoid arthritis and various tumours. We sought to elucidate the mechanism underlying MTX\u2010induced hepatotoxicity and establish a potentially effective intervention strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We administered MTX to liver cells and mice and assessed hepatotoxicity by cell viability assay and hepatic pathological changes. We determined ferroptosis and ferritinophagy by detecting ferroptosis\u2010related markers and autophagic degradation of ferritin heavy chain 1 (FTH1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We have shown that hepatocytes treated with MTX undergo ferroptosis, and this process can be attenuated by ferroptosis inhibitors. Interestingly, NCOA4\u2010mediated ferritinophagy was found to be involved in MTX\u2010induced ferroptosis, which was demonstrated by the relief of ferroptosis through the inhibition of autophagy or knockdown of\n                      <jats:italic>Ncoa4<\/jats:italic>\n                      . Furthermore, MTX treatment resulted in the elevation of high\u2010mobility group box\u00a01 (HMGB1) expression. The depletion of\n                      <jats:italic>Hmgb1<\/jats:italic>\n                      in hepatocytes considerably alleviated MTX\u2010induced hepatotoxicity by limiting autophagy and the subsequent autophagy\u2010dependent ferroptosis. It is noteworthy that glycyrrhizic acid (GA), a precise inhibitor of HMGB1, effectively suppressed autophagy, ferroptosis and hepatotoxicity caused by MTX.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study shows the significant roles of autophagy\u2010dependent ferroptosis and HMGB1 in MTX\u2010induced hepatotoxicity. It emphasizes that the inhibition of ferritinophagy and HMGB1 may have potential as a therapeutic approach for preventing and treating MTX\u2010induced liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15811","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T15:00:51Z","timestamp":1702393251000},"page":"691-705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ferritinophagy\u2010mediated ferroptosis facilitates methotrexate\u2010induced hepatotoxicity by high\u2010mobility group box\u00a01 (\n                    <scp>HMGB1<\/scp>\n                    )"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9968-4029","authenticated-orcid":false,"given":"Chengbo","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Pediatric Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maodong","family":"Leng","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital  Zhengzhou Henan 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