{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:38:53Z","timestamp":1790948333424,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T00:00:00Z","timestamp":1699747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY22H020005"],"award-info":[{"award-number":["LY22H020005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["82073843"],"award-info":[{"award-number":["82073843"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["81873466"],"award-info":[{"award-number":["81873466"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LY22H020005"],"award-info":[{"award-number":["LY22H020005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073843"],"award-info":[{"award-number":["82073843"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873466"],"award-info":[{"award-number":["81873466"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Doxorubicin (DOX) is a broad-spectrum antineoplastic agent that widely used in clinic. However, its application is largely limited by its toxicity in multiple organs. Fibroblast growth factor 1 (FGF1) showed protective potential in various liver diseases, but the role of endogenous FGF1 in DOX-induced liver damage is currently unknown. Both wild-type (WT) and FGF1 knockout (FGF1-KO) mice were treated with DOX. DOX induced loss of body weight and liver weight and elevation of ALT and AST in WT mice, which were aggravated by FGF1 deletion. FGF1 deletion exacerbated hepatic oxidative stress mirrored by further elevated 3-nitrosative modification of multiple proteins and malondialdehyde content. These were accompanied by blunted compensatively antioxidative responses indicated by impaired upregulation of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant gene expression. The aggravated oxidative stress was coincided with exacerbated cell apoptosis in DOX-treated FGF1-KO mice reflected by further increased TUNEL positive cell staining and BCL-2-associated X expression and caspase 3 cleavage. These detrimental changes in DOX-treated FGF1-KO mice were associated with worsened intestinal fibrosis and increased upregulation fibrotic marker connective tissue growth factor and \u03b1-smooth muscle actin expression. However, DOX-induced hepatic inflammatory responses were not further affected by FGF1 deletion. These results demonstrate that endogenous FGF1 deficiency aggravates DOX-induced liver damage and FGF1 is a potential therapeutic target for treatment of DOX-associated hepatoxicity.<\/jats:p>","DOI":"10.3390\/toxics11110925","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:44:27Z","timestamp":1699865067000},"page":"925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Endogenous FGF1 Deficiency Aggravates Doxorubicin-Induced Hepatotoxicity"],"prefix":"10.3390","volume":"11","author":[{"given":"Chunjie","family":"Gu","sequence":"first","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjian","family":"Li","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yi","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeng","family":"Wang","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"},{"name":"Department of Clinical Translational Research, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Fan","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-9951","authenticated-orcid":false,"given":"Da","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Wenzhou University, Wenzhou 325200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"},{"name":"Department of Clinical Translational Research, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Yan","sequence":"additional","affiliation":[{"name":"The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guicheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing 404000, China"},{"name":"Chongqing Municipality Clinical Research Center for Endocrine and Metabolic Diseases, Chongqing 400015, China"},{"name":"School of Medicine, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,12]]},"reference":[{"key":"ref_1","first-page":"2435","article-title":"ERK1\/2\/p53 and NF-kappaB dependent-PUMA activation involves in doxorubicin-induced cardiomyocyte apoptosis","volume":"20","author":"Zhang","year":"2016","journal-title":"Eur. 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