Exploration of the underlying mechanisms of isoniazid/rifampicin‐induced liver injury in mice using an integrated proteomics and metabolomics approach. Issue 12 (16th September 2022)

• Record Type: Journal Article
• Authors: Song, Yanqing; Qu, Xiaoyu; Tao, Lina; Gao, Huan; Zhang, Yueming; Zhai, Jinghui; Gong, Jiawei; Hu, Tingting
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 36:Issue 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-16
• Subjects: isoniazid -- liver injury -- metabolomics -- proteomics -- rifampicin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.23217
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: The hepatotoxic mechanism resulting from coadministration of isoniazid (INH) and rifampicin (RIF) are complex and studies remain inconclusive. To systematically explore the underlying mechanisms, an integrated mass‐based untargeted metabolomics and label‐free quantitative proteomics approach was used to clarify the mechanism of INH/RIF‐induced liver injury. Thirty male mice were randomly divided into three groups: control (receiving orally administered vehicle solution), INH (150 mg/kg) + RIF (300 mg/kg) orally administered for either 7 or 14 days, respectively. Serum was collected for the analysis of biochemical parameters and liver samples were obtained for mass spectrum‐based 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.