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To systematically explore the underlying mechanisms, an integrated mass\u2010based untargeted metabolomics and label\u2010free quantitative proteomics approach was used to clarify the mechanism of INH\/RIF\u2010induced liver injury. Thirty male mice were randomly divided into three groups: control (receiving orally administered vehicle solution), INH (150\u2009mg\/kg)\u2009+\u2009RIF (300\u2009mg\/kg) orally administered for either 7\u00a0or 14 days, respectively. Serum was collected for the analysis of biochemical parameters and liver samples were obtained for mass\u00a0spectrum\u2010based proteomics, metabolomics, and lipidomics analysis. Overall, 511 proteins, 31 metabolites, and 23 lipids were dysregulated and identified, and disordered biological pathways were identified. The network of integrated multiomics showed that glucose, lipid, and amino acid metabolism as well as energy metabolism were mainly dysregulated and led to oxidative stress, inflammation, liver steatosis, and cell death induced by INH and RIF. Coadministration of INH and RIF can induce liver injury by oxidative stress, inflammation, liver steatosis, and cell death, and the reduction in glutathione levels may play a critical role in these systematic changes and warrants further study.<\/jats:p>","DOI":"10.1002\/jbt.23217","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T10:51:40Z","timestamp":1663325500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exploration of the underlying mechanisms of isoniazid\/rifampicin\u2010induced liver injury in mice using an integrated proteomics and metabolomics approach"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-3342","authenticated-orcid":false,"given":"Yanqing","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1685-6914","authenticated-orcid":false,"given":"Xiaoyu","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-841X","authenticated-orcid":false,"given":"Huan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7707-7928","authenticated-orcid":false,"given":"Jinghui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14896"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.15766\/mep_2374-8265.11143"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2083-4"},{"key":"e_1_2_8_5_1","first-page":"e920350","volume":"26","author":"Zhao H.","year":"2020","journal-title":"Med. 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