{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:03:42Z","timestamp":1787137422139,"version":"build-2736575974"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH014"],"award-info":[{"award-number":["ZR2022MH014"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoimmune hepatitis (AIH) is an autoimmune disease mediated by abnormal autoimmune. The pathogenesis and pathological manifestation of immune-mediated liver injury, induced by concanavalin A (ConA) in mice, closely parallel those observed in human AIH. However, the sensitivity and stability of mice to ConA vary depending on the strain and sex of the mice. Therefore, this study aimed to compare the sensitivity and stability of Balb\/c, C57BL\/6J, and ICR mice to ConA-induced acute liver injury. In this study, the mice in ConA group were injected with ConA (15\u00a0mg\/kg\u00b7bw) via tail vein. After 8\u00a0h, the blood, liver, and spleen were collected for subsequent analysis. The liver index of Balb\/c mice was increased (P\u2009&amp;lt;\u20090.05). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels of male C57BL\/6J mice in ConA-treated group were the highest among the three strains of mice, followed by female Balb\/c mice (P\u2009&amp;lt;\u20090.05). After ConA challenge, ICR, Balb\/c, and C57BL\/6J mice (both male and female) appeared markedly inflammatory cell infiltration and hepatocyte necrosis. Furthermore, hemorrhagic necrosis is more severe in females than in males. Lastly, male C57BL\/6J and female Balb\/c mice had the lowest coefficient of variation in serum ALT, AST, and LDH activities, while female Balb\/c mice had the minimum coefficient of variation of the liver index, suggesting that they have good stability to ConA. Altogether, our study found that Balb\/c female and C57BL\/6J male mice have high sensitivity and good stability to ConA challenge, which were suitable for mimicking the pathology of AIH in humans.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf036","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T13:24:07Z","timestamp":1742217847000},"source":"Crossref","is-referenced-by-count":4,"title":["Sensitivity and stability of Balb\/c, C57BL\/6J, and ICR mice to the acute liver injury induced by concanavalin A"],"prefix":"10.1093","volume":"14","author":[{"given":"Mingjie","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Kou","sequence":"additional","affiliation":[{"name":"Experimental Center for Public Health and Preventive Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Experimental Center for Public Health and Preventive Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Ma","sequence":"additional","affiliation":[{"name":"Experimental Center for Public Health and Preventive Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-2059","authenticated-orcid":false,"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-7364","authenticated-orcid":false,"given":"Cuili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University , 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"2025031713235107900_ref1","doi-asserted-by":"publisher","first-page":"18017","DOI":"10.1038\/nrdp.2018.17","article-title":"Autoimmune hepatitis","volume":"4","author":"Mieli-Vergani","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2025031713235107900_ref2","doi-asserted-by":"publisher","first-page":"108411","DOI":"10.1016\/j.intimp.2021.108411","article-title":"Pathogenesis of Concanavalin a induced autoimmune hepatitis in mice","volume":"102","author":"Hao","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"2025031713235107900_ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cld.2023.06.002","article-title":"Autoimmune hepatitis: epidemiology, subtypes, and presentation","volume":"28","author":"Shiffman","year":"2024","journal-title":"Clin Liver Dis"},{"key":"2025031713235107900_ref4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cld.2023.06.003","article-title":"Autoimmune hepatitis: pathophysiology","volume":"28","author":"Yuming","year":"2024","journal-title":"Clin Liver Dis"},{"key":"2025031713235107900_ref5","doi-asserted-by":"publisher","first-page":"e458","DOI":"10.1097\/HC9.0000000000000458","article-title":"Autoimmune hepatitis: current and future therapies","volume":"8","author":"Reau","year":"2024","journal-title":"Hepatol Commun"},{"key":"2025031713235107900_ref6","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3350\/cmh.2020.0189","article-title":"Recent updates on the management of autoimmune hepatitis","volume":"27","author":"Komori","year":"2021","journal-title":"Clin Mol Hepatol"},{"key":"2025031713235107900_ref7","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1172\/JCI115836","article-title":"A T cell-dependent experimental liver injury in mice inducible by concanavalin a","volume":"90","author":"Tiegs","year":"1992","journal-title":"J Clin Invest"},{"key":"2025031713235107900_ref8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1515\/biol-2022-0013","article-title":"Concanavalin A-induced autoimmune hepatitis model in mice: mechanisms and future outlook","volume":"17","author":"Liu","year":"2022","journal-title":"Open Life Sci"},{"key":"2025031713235107900_ref9","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1177\/0023677215572841","article-title":"The concanavalin a model of acute hepatitis in mice","volume":"49","author":"Heymann","year":"2015","journal-title":"Lab Anim-Uk"},{"key":"2025031713235107900_ref10","doi-asserted-by":"publisher","first-page":"103583","DOI":"10.1016\/j.autrev.2024.103583","article-title":"Remodeling of T-cell mitochondrial metabolism to treat autoimmune diseases","volume":"23","author":"Lin","year":"2024","journal-title":"Autoimmun Rev"},{"key":"2025031713235107900_ref11","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/imm.13718","article-title":"Tregs protect against invariant NKT cell-mediated autoimmune colitis and hepatitis","volume":"171","author":"Venken","year":"2024","journal-title":"Immunology"},{"key":"2025031713235107900_ref12","doi-asserted-by":"publisher","first-page":"103162","DOI":"10.1016\/j.jaut.2023.103162","article-title":"Silencing of aryl hydrocarbon receptor repressor restrains Th17 cell immunity in autoimmune hepatitis","volume":"143","author":"Gao","year":"2024","journal-title":"J Autoimmun"},{"key":"2025031713235107900_ref13","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1177\/026119290803600310","article-title":"Estimates for worldwide laboratory animal use in 2005","volume":"36","author":"Taylor","year":"2008","journal-title":"Altern Lab Anim"},{"key":"2025031713235107900_ref14","doi-asserted-by":"publisher","first-page":"383","DOI":"10.4049\/jimmunol.1700453","article-title":"Of mice, dirty mice, and men: using mice to understand human immunology","volume":"199","author":"Masopust","year":"2017","journal-title":"J Immunol"},{"key":"2025031713235107900_ref15","doi-asserted-by":"publisher","first-page":"382","DOI":"10.3390\/diagnostics14040382","article-title":"Autoimmune hepatitis: a diagnostic and therapeutic overview","volume":"14","author":"Mercado","year":"2024","journal-title":"Diagnostics (Basel)"},{"key":"2025031713235107900_ref16","doi-asserted-by":"publisher","first-page":"7815","DOI":"10.1007\/s11033-023-08666-0","article-title":"Biomarkers of liver diseases","volume":"50","author":"Tamber","year":"2023","journal-title":"Mol Biol Rep"},{"key":"2025031713235107900_ref17","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.7150\/thno.82607","article-title":"Hepatocyte HSPA12A inhibits macrophage chemotaxis and activation to attenuate liver ischemia\/reperfusion injury via suppressing glycolysis-mediated HMGB1 lactylation and secretion of hepatocytes","volume":"13","author":"Du","year":"2023","journal-title":"Theranostics"},{"key":"2025031713235107900_ref18","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1080\/15563650.2023.2259089","article-title":"Novel biomarkers for drug-induced liver injury","volume":"61","author":"Humphries","year":"2023","journal-title":"Clin Toxicol (Phila)"},{"key":"2025031713235107900_ref19","doi-asserted-by":"publisher","first-page":"154484","DOI":"10.1016\/j.phymed.2022.154484","article-title":"Koumine regulates macrophage M1\/M2 polarization via TSPO, alleviating sepsis-associated liver injury in mice","volume":"107","author":"Jin","year":"2022","journal-title":"Phytomedicine"},{"key":"2025031713235107900_ref20","doi-asserted-by":"publisher","first-page":"1320758","DOI":"10.3389\/fcimb.2023.1320758","article-title":"Clinical features and risk factors of liver injury in patients with chlamydia psittaci pneumonia- a retrospective analysis","volume":"13","author":"Guo","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"2025031713235107900_ref21","doi-asserted-by":"publisher","first-page":"3309","DOI":"10.1007\/s00436-014-3994-6","article-title":"Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis","volume":"113","author":"Nascimento","year":"2014","journal-title":"Parasitol Res"},{"key":"2025031713235107900_ref22","first-page":"3389","article-title":"Secoemestrin C inhibits activation of NKT\/conventional T cells and protects against concanavalin A-induced autoimmune hepatitis in mice","volume":"12","author":"Tan","year":"2020","journal-title":"Am J Transl Res"},{"key":"2025031713235107900_ref23","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1111\/liv.12251","article-title":"Non-invasive markers of inflammation in autoimmune hepatitis","volume":"33","author":"Fabbri","year":"2013","journal-title":"Liver Int"},{"key":"2025031713235107900_ref24","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.3748\/wjg.v27.i35.5919","article-title":"Liver-spleen axis dysfunction in COVID-19","volume":"27","author":"Cococcia","year":"2021","journal-title":"World J Gastroenterol"},{"key":"2025031713235107900_ref25","doi-asserted-by":"publisher","first-page":"eaau6085","DOI":"10.1126\/sciimmunol.aau6085","article-title":"Structure and function of the immune system in the spleen","volume":"4","author":"Lewis","year":"2019","journal-title":"Sci Immunol"},{"key":"2025031713235107900_ref26","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1038\/s41598-020-61006-1","article-title":"Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in lipopolysaccharide\/Concanavalin a -induced murine models of inflammation","volume":"10","author":"Abu-Rish","year":"2020","journal-title":"Sci Rep"},{"key":"2025031713235107900_ref27","doi-asserted-by":"publisher","first-page":"199","DOI":"10.7150\/ijbs.65402","article-title":"RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism","volume":"18","author":"Liu","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2025031713235107900_ref28","doi-asserted-by":"publisher","first-page":"1142723","DOI":"10.3389\/fimmu.2023.1142723","article-title":"Sex and gender influence on immunity and autoimmunity","volume":"14","author":"Lahita","year":"2023","journal-title":"Front Immunol"},{"key":"2025031713235107900_ref29","doi-asserted-by":"publisher","first-page":"1049665","DOI":"10.3389\/fendo.2022.1049665","article-title":"Thyroid autoimmunity and its negative impact on female fertility and maternal pregnancy outcomes","volume":"13","author":"Tanska","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025031713235107900_ref30","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"2025031713235107900_ref31","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1126\/science.abe7199","article-title":"Sex differences in immune responses","volume":"371","author":"Takahashi","year":"2021","journal-title":"Science"},{"key":"2025031713235107900_ref32","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41577-024-00996-9","article-title":"The conneXion between sex and immune responses","volume":"24","author":"Forsyth","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"2025031713235107900_ref33","doi-asserted-by":"publisher","first-page":"739757","DOI":"10.3389\/fimmu.2021.739757","article-title":"Sex-related differences in innate and adaptive immune responses to SARS-CoV-2","volume":"12","author":"Agrawal","year":"2021","journal-title":"Front Immunol"},{"key":"2025031713235107900_ref34","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3390\/jpm12060925","article-title":"Gender and autoimmune liver diseases: relevant aspects in clinical practice","volume":"12","author":"Invernizzi","year":"2022","journal-title":"J Pers Med"},{"key":"2025031713235107900_ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trsl.2022.04.006","article-title":"Gender-sex differences in autoimmune atrophic gastritis","volume":"248","author":"Lahner","year":"2022","journal-title":"Transl Res"},{"key":"2025031713235107900_ref36","doi-asserted-by":"publisher","first-page":"102468","DOI":"10.1016\/j.autrev.2020.102468","article-title":"Estrogen, estrogen-like molecules and autoimmune diseases","volume":"19","author":"Merrheim","year":"2020","journal-title":"Autoimmun Rev"},{"key":"2025031713235107900_ref37","doi-asserted-by":"publisher","first-page":"103996","DOI":"10.1016\/j.cellimm.2019.103996","article-title":"Matters of life and death: how estrogen and estrogen receptor binding to the immunoglobulin heavy chain locus may influence outcomes of infection, allergy, and autoimmune disease","volume":"346","author":"Jones","year":"2019","journal-title":"Cell Immunol"},{"key":"2025031713235107900_ref38","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4415\/ANN_16_02_12","article-title":"Sex-based differences in autoimmune diseases","volume":"52","author":"Ortona","year":"2016","journal-title":"Ann Ist Super Sanita"},{"key":"2025031713235107900_ref39","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.3389\/fimmu.2018.02279","article-title":"Sex hormones in acquired immunity and autoimmune disease","volume":"9","author":"Moulton","year":"2018","journal-title":"Front Immunol"},{"key":"2025031713235107900_ref40","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1126\/science.1233521","article-title":"Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity","volume":"339","author":"Markle","year":"2013","journal-title":"Science"},{"key":"2025031713235107900_ref41","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jaut.2018.05.008","article-title":"Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex","volume":"92","author":"Rizzetto","year":"2018","journal-title":"J Autoimmun"},{"key":"2025031713235107900_ref42","doi-asserted-by":"publisher","first-page":"20230823","DOI":"10.1515\/med-2023-0823","article-title":"The progress of autoimmune hepatitis research and future challenges","volume":"18","author":"Zhang","year":"2023","journal-title":"Open Med (Wars)"},{"key":"2025031713235107900_ref43","doi-asserted-by":"publisher","first-page":"4874","DOI":"10.7150\/thno.97427","article-title":"Engaging natural regulatory myeloid cells to restrict T-cell hyperactivation-induced liver inflammation via extracellular vesicle-mediated purine metabolism regulation","volume":"14","author":"Yang","year":"2024","journal-title":"Theranostics"},{"key":"2025031713235107900_ref44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s43556-021-00049-w","article-title":"The molecular mechanism of acute liver injury and inflammatory response induced by Concanavalin a","volume":"2","author":"Liu","year":"2021","journal-title":"Mol Biomed"},{"key":"2025031713235107900_ref45","doi-asserted-by":"publisher","first-page":"114149","DOI":"10.1016\/j.intimp.2025.114149","article-title":"Allyl methyl disulfide attenuates liver injury induced by concanavalin a by suppressing M1 polarization of macrophages and NLRP3 inflammasome activation","volume":"149","author":"Song","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"2025031713235107900_ref46","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2298\/ABS190121016L","article-title":"Eugenol attenuates concanavalin A-induced hepatitis through modulation of cytokine levels and inhibition of mitochondrial oxidative stress","volume":"71","author":"Liu","year":"2019","journal-title":"Arch Biol Sci"},{"key":"2025031713235107900_ref47","doi-asserted-by":"publisher","first-page":"e547","DOI":"10.1002\/cpz1.547","article-title":"Using the collaborative cross and diversity outbred mice in immunology","volume":"2","author":"Hackett","year":"2022","journal-title":"Curr Protoc"},{"key":"2025031713235107900_ref48","doi-asserted-by":"publisher","first-page":"115379","DOI":"10.1016\/j.taap.2020.115379","article-title":"Autoantibodies in outbred Swiss Webster mice following exposure to gold and mercury","volume":"412","author":"Amirhosseini","year":"2021","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025031713235107900_ref49","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41592-018-0224-7","article-title":"Comparing phenotypic variation between inbred and outbred mice","volume":"15","author":"Tuttle","year":"2018","journal-title":"Nat Methods"},{"key":"2025031713235107900_ref50","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1093\/ilar\/ilu036","article-title":"Evidence should trump intuition by preferring inbred strains to outbred stocks in preclinical research","volume":"55","author":"Festing","year":"2014","journal-title":"ILAR J"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/2\/tfaf036\/62428387\/tfaf036.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/2\/tfaf036\/62428387\/tfaf036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T13:24:10Z","timestamp":1742217850000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfaf036\/8081712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfaf036","relation":{},"ISSN":["2045-4538"],"issn-type":[{"value":"2045-4538","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,3,1]]},"article-number":"tfaf036"}}