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However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra\u2010high\u2010performance liquid chromatography\u2013tandem mass spectrometry (UHPLC\u2010MS\/MS)\u2010based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD\u2010induced hepatotoxicity in rats. Sixteen male and female Sprague\u2013Dawley rats were randomly divided into two groups: control and CTD (1.0\u00a0mg\/kg) groups. Serum and liver samples were collected after 28\u2009days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD\u2010induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite\u2013gene\u2013enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD\u2010induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC\u2010MS\/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD\u2010induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jat.4267","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T20:13:23Z","timestamp":1638735203000},"page":"970-980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4963-6109","authenticated-orcid":false,"given":"Weina","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmacy Zunyi Medical University  Zunyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Zunyi Medical University  Zunyi 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