Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism
Related Experiment Video
Updated: Oct 11, 2025

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
Weina Cheng1, Yazhi Wang1, Jingxian Liu2
1School of Pharmacy, Zunyi Medical University, Zunyi, China.
Abstract:
Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague-Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite-gene-enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced 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-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced 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-induced hepatotoxicity.
More Related Videos
10:12Isolation and 3D Collagen Sandwich Culture of Primary Mouse Hepatocytes to Study the Role of Cytoskeleton in Bile Canalicular Formation In Vitro
Published on: December 20, 2019
08:42Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
Related Concept Videos
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Hepatic Drug Excretion: Influencing Factors
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug