Illuminating the hepatotoxic mechanism of norcantharidin in rats using metabolomics analysis

Abstract Background Norcantharidin (NCTD) has multiple antitumor effects. However, NCTD can induce significant hepatotoxicity and the mechanism of hepatotoxicity is not clear for now. Objective This study aimed to explore the hepatotoxicity of NCTD in rat by ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight (Q-TOF)-MS (UPLC/Q-TOF-MS) metabolomics. Results Serum biochemical indices including alanine aminotransferase (ALT) and total bilirubin (T-BIL) were significantly increased. Histopathological and ultrastructure results revealed that hepatocytes were damaged. Furthermore, the metabolomics results showed that 11 metabolites in serum and 8 metabolites in liver were differential metabolites for NCTD hepatotoxicity. Four metabolic pathways including the sphingolipid metabolism, purine metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were the key metabolic pathways related to NCTD hepatotoxicity. Conclusion The metabolomics analysis in this study reveal new clues on the hepatotoxicity mechanism of NCTD in rats. These findings have potential applications in the toxicity study of NCTD.