{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:26:46Z","timestamp":1792009606024,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Drug\u2010induced hepatotoxicity (DIH) is a serious adverse effect of Antituberculosis (anti\u2010TB) therapy, frequently causing treatment interruption and poor outcomes. This study combines network toxicology, molecular docking technology, and in vivo experiments to clarify the molecular mechanisms of anti\u2010TB drug\u2010induced hepatotoxicity. We identified key molecular targets and signaling pathways associated with hepatotoxicity by integrating drug\u2010disease intersection\u2010target interactions and pathway enrichment analyses. Molecular docking assessed the binding affinity between Antituberculosis drugs (e.g., isoniazid, rifampicin, pyrazinamide) and hub targets, with in vivo experiments further validating changes in mRNA expression of these core targets. Our findings suggest that NFE2L2, NFKB1, MAP2K1, MAPK14, IGF1R, and GSK3B may represent important targets for antituberculosis drug\u2010induced hepatotoxicity, with oxidative stress, apoptosis, and lipid accumulation potentially serving as underlying mechanisms. These insights deepen our understanding of the molecular basis of anti\u2010TB drug\u2010induced hepatotoxicity and suggest potential targets for developing hepatoprotective strategies during tuberculosis treatment.<\/jats:p>","DOI":"10.1002\/jbt.70602","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:10:45Z","timestamp":1762845045000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Network Toxicology and Molecular Docking Analysis of Antituberculosis Drug\u2010Induced Hepatotoxicity"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2213-9272","authenticated-orcid":false,"given":"Rui","family":"Liu","sequence":"first","affiliation":[{"name":"Institute for Immunology and Pathogenesis Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, School of Medicine Chongqing University Chongqing China"},{"name":"Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yancheng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Power Transmission Equipment Technology, School of Electrical Engineering Chongqing University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30308-3"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-074866"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00436-2015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/650576"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23386"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02637-17"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2022.153256"},{"issue":"2","key":"e_1_2_11_9_1","first-page":"31","article-title":"Network Toxicology: A New Science","volume":"6","author":"WenJun Z.","year":"2016","journal-title":"Computational Ecology and Software"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413255"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac956"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae303"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae236"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz382"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx374"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac297"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1151"},{"issue":"1","key":"e_1_2_11_19_1","first-page":"845","article-title":"The DisGeNET Knowledge Platform for Disease Genomics: 2019 Update","volume":"48","author":"Pi\u00f1ero J.","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1077"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408688"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15091130"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1666ST"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1037814"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.06.020"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.07.038"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00854-16"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106634"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-019-0266-0"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21799"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165787"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01866-12"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053010"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-024-09974-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)70168-6"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1457010"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.09.140"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70602","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70602","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:26:51Z","timestamp":1785436011000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jbt.70602"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70602","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70602"}}