{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:10:25Z","timestamp":1787015425980,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LYY19H310007"],"award-info":[{"award-number":["LYY19H310007"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["Y20190653"],"award-info":[{"award-number":["Y20190653"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Crizotinib (CRIZO) has been widely employed to treat non\u2010small\u2010cell lung cancer. However, hepatic inflammatory injury is the major toxicity of CRIZO, which limits its clinical application, and the underlying mechanism of CRIZO\u2010induced hepatotoxicity has not been fully explored. Herein, we used cell counting kit\u20108 assay and flow cytometry to detect CRIZO\u2010induced cytotoxicity on human hepatocytes (HL\u20107702). CRIZO significantly reduced the survival rate of hepatocytes in a dose\u2010dependent manner. Furthermore, the reactive oxygen species (ROS) assay kit showed that CRIZO treatment strongly increased the level of ROS. In addition, CRIZO treatment caused the appearance of balloon\u2010like bubbles and autophagosomes in HL\u20107702 cells. Subsequently, Western blotting, quantitative real\u2010time PCR and ELISA assays revealed that ROS\u2010mediated pyroptosis and autophagy contributed to CRIZO\u2010induced hepatic injury. Based on the role of ROS in CRIZO\u2010induced hepatotoxicity, magnesium isoglycyrrhizinate (MgIG) was used as an intervention drug. MgIG activated the Nrf2\/HO\u20101 signalling pathway and reduced ROS level. Additionally, MgIG suppressed hepatic inflammation by inhibiting NF\u2010\u03baB activity, thereby reducing CRIZO\u2010induced hepatotoxicity. In conclusion, CRIZO promoted autophagy activation and pyroptosis via the accumulation of ROS in HL\u20107702 cells. MgIG exerts therapeutic effects on CRIZO\u2010induced hepatotoxicity by decreasing the level of ROS.<\/jats:p>","DOI":"10.1111\/jcmm.17474","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T02:45:10Z","timestamp":1658285110000},"page":"4492-4505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>MgIG<\/scp>\n                    exerts therapeutic effects on crizotinib\u2010induced hepatotoxicity by limiting\n                    <scp>ROS<\/scp>\n                    \u2010mediated autophagy and pyroptosis"],"prefix":"10.1111","volume":"26","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaolin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjiang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research Center The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0294-7399","authenticated-orcid":false,"given":"Ziye","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Research Center The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0142-z"},{"key":"e_1_2_10_3_1","unstructured":"FDA instructions for crizotinib. 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