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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
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Published on: May 10, 2016

Cantharidin Causes Hepatotoxicity by Disrupting GSH-Mediated Redox Homeostasis

Hong Tang1,2,3, Qing Rao1,4,5, Ting Liu1,4

  • 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Guizhou Medical University, Guiyang, China.

Journal of Applied Toxicology : JAT
|August 23, 2026
PubMed

Insights

Cantharidin (CTD) causes liver damage by disrupting glutathione metabolism and inducing oxidative stress and apoptosis. Exogenous glutathione (GSH) supplementation can protect against CTD-induced hepatotoxicity.

Area of Science:

  • Biochemistry
  • Toxicology
  • Molecular Biology

Background:

  • Cantharidin (CTD) exhibits potent anticancer properties but is limited by significant hepatotoxicity.
  • The precise molecular mechanisms underlying CTD-induced liver injury remain incompletely understood.
  • Further investigation is crucial to elucidate CTD's toxicological pathways and identify potential interventions.

Purpose of the Study:

  • To investigate the molecular mechanisms of CTD-induced hepatotoxicity.
  • To evaluate the protective effects of exogenous glutathione (GSH) against CTD-induced liver injury.

Main Methods:

  • In vitro studies using hepatocytes to assess oxidative stress markers, mitochondrial function, and apoptosis-related protein expression.
  • In vivo experiments in animal models to evaluate hepatic glutathione levels, enzyme activities, and CTD-induced pathological changes.
  • Assessment of glutamate-cysteine ligase (GCL) subunit expression (GCLC and GCLM) under CTD exposure.

Main Results:

  • CTD exposure reduced the GSH/GSSG ratio, catalase (CAT), and glutathione peroxidase (GPX) activities, while increasing malondialdehyde (MDA) and superoxide dismutase (SOD) in vitro.
  • CTD downregulated GCLM expression, decreased mitochondrial membrane potential (MMP), and induced apoptosis by altering Bcl-2 family proteins and caspase activation.
  • In vivo, CTD decreased hepatic GSH and Cys levels and downregulated GCLC expression, with minimal changes in GCLM and cytochrome c (Cyt c).
  • Exogenous GSH (in vitro) and GSH intervention (in vivo) effectively mitigated CTD-induced oxidative damage.

Conclusions:

  • CTD induces hepatotoxicity through disruption of GSH metabolic homeostasis, oxidative stress, and mitochondrial dysfunction, ultimately triggering hepatocellular apoptosis.
  • CTD exhibits divergent effects on GCL subunit expression in vitro and in vivo.
  • Exogenous GSH supplementation demonstrates a protective role against CTD-induced liver injury, suggesting a potential therapeutic strategy.
Keywords:
GCL subunitsGSH depletionapoptosiscantharidinhepatotoxicityoxidative stress

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