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Updated: Aug 27, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

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Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

Maud Maillard1,2, Cécile Arellano1, Christelle Vachoux1

  • 1Centre de Recherches en Cancérologie de Toulouse, Université de Toulouse, Inserm, Université Toulouse III-Paul Sabatier, 2 Avenue Hubert Curien, CS53717, CEDEX 1, 31037 Toulouse, France.

Metabolites
|September 23, 2022
PubMed

Insights

Aldehyde derivatives of pazopanib (P-CHO) and sunitinib (S-CHO) were investigated for their role in drug-induced liver injury. These compounds were found to impair hepatocyte function, suggesting their involvement in tyrosine kinase inhibitor hepatotoxicity.

Area of Science:

  • Pharmacology
  • Hepatology
  • Toxicology

Background:

  • Pazopanib and sunitinib are tyrosine kinase inhibitors used for advanced renal cell carcinoma.
  • These drugs are associated with an increased risk of drug-induced liver injury (DILI).
  • Aldehyde metabolites (P-CHO and S-CHO) of pazopanib and sunitinib have been identified in liver microsomes.

Purpose of the Study:

  • To investigate the role of P-CHO and S-CHO in pazopanib and sunitinib-induced hepatotoxicity.
  • To evaluate the effects of these aldehyde derivatives on hepatic cell lines.
  • To assess the presence of P-CHO in patients treated with pazopanib.

Main Methods:

  • Treatment of HepG2 and HepaRG hepatic cell lines with P-CHO and S-CHO.
  • Evaluation of cell viability, mitochondrial dysfunction, and oxidative stress.
  • Measurement of plasma P-CHO concentrations in patients receiving pazopanib.

Main Results:

  • S-CHO showed a modest decrease in HepG2 cell viability and affected mitochondrial respiratory capacity.
  • P-CHO significantly reduced HepG2 cell viability and ATP production.
  • P-CHO was detected in the plasma of patients treated with pazopanib.

Conclusions:

  • P-CHO and S-CHO negatively impact hepatocyte integrity and function.
  • These aldehyde metabolites are potentially involved in the hepatotoxicity associated with pazopanib and sunitinib treatment.
  • Further investigation into these metabolites is warranted to understand and mitigate drug-induced liver injury.
Keywords:
aldehydehepatotoxicitypazopanibreactive metabolitessunitinib

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