Background
Cantharidin (CTD), the main toxic component of Mylabris, has been extensively used for tumor treatment in recent years. CTD-induced liver toxicity has attracted significant interest in clinic.
Methods
In this study, biochemical parameters and liver pathological changes were analyzed after CTD was administered to mice by gavage. Subsequently, a lipidomic approach was used to investigate serum lipid metabolism disorders, and the mechanism underlying CTD-induced liver injury in mice was explored.
Results
The results showed that the levels of TC and LDL-C were significantly increased after CTD intervention. Besides, pathological results showed inflammatory cell infiltration and hepatocyte necrosis in the liver. Furthermore, lipidomics found that a total of 18 lipid metabolites were increased and 40 were decreased, including LPC(20:4), LPC(20:3), PC(22:6e/2:0), PE(14:0e/21:2), PC(18:2e/22:6), glycerophospholipids, CE(16:0), CE(18:0) Cholesterol esters and TAG(12:0/12:0/22:3), TAG(16:1/16:2/20:4), TAG(18:1/18:1/20:0), TAG(16:2/18:2/18:2), TAG(18:0/18:0/20:0), TAG(13:1/19:0/19:0) glycerolipids. Metabolic pathway analysis found that glycerophospholipid, glycerol ester and glycosylphosphatidylinositol (GPI)-anchored biosynthetic metabolic pathways were dysregulated and the increase in PE caused by glycophoric metabololism and GPI may be the source of lipid metabolism disorders caused by CTD. Overall, the present study provided new insights into the mechanism of CTD-induced liver injury and increased drug safety during clinical application.