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Updated: Jun 8, 2025

Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
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Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics

Published on: November 29, 2024

465

Metabolomics reveals that sulfotransferase 1 may regulate colchicine-induced liver injury

Ruoyue Huang1, Chunyan Wang1, Zhanxuan E Wu1

  • 1Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-related Molecular Network, And State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, China.

Chemico-Biological Interactions
|November 4, 2024
PubMed

Insights

Colchicine overdose can harm the liver by reducing beneficial sulfated metabolites. Restoring these metabolites or targeting the SULT1 enzyme may prevent colchicine-induced liver injury.

Area of Science:

  • Hepatology
  • Pharmacology
  • Metabolomics

Background:

  • Colchicine is a common gout treatment.
  • Colchicine overdose can cause liver damage, but the mechanism is unknown.
  • Understanding colchicine hepatotoxicity is crucial for patient safety.

Purpose of the Study:

  • To investigate the mechanism of colchicine-induced liver injury.
  • To identify colchicine metabolites and their effect on endogenous metabolites.
  • To explore potential therapeutic strategies against colchicine hepatotoxicity.

Main Methods:

  • In vivo investigation of colchicine hepatotoxicity.
  • Ultra High Performance Liquid Chromatography-mass spectrometry (UHPLC-MS) for metabolomic analysis.
  • Investigating the role of sulfotransferase 1 (SULT1) and its regulation.

Main Results:

  • Seventeen colchicine metabolites identified, including three novel sulfated forms.
  • Colchicine decreased endogenous sulfated metabolites, potentially via SULT1 and PPARα.
  • Inhibition of SULT1 worsened liver injury; activation or supplementation with indoxyl sulfate (IS) or p-cresol sulfate (PCS) alleviated it.

Conclusions:

  • Colchicine may cause liver injury by inhibiting SULT1, decreasing bioactive sulfated metabolites (IS and PCS).
  • Targeting SULT1 and administering IS/PCS show potential for preventing colchicine hepatotoxicity.
  • This study offers insights into therapeutic targets for colchicine-induced liver damage.
Keywords:
ColchicineLiver injuryMass spectrometryMetabolomics analysisSulfotransferase

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