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[Colchicinoids--their toxicity and biological activity]

P Ondra1, J Ulrichová

  • 1Institut für Gerichtsmedizin und medizinisches Recht, Medizinische Fakultät, Palacký Universität, Olomouc, Ischechische Republik.

Acta Universitatis Palackianae Olomucensis Facultatis Medicae
|January 1, 1995
PubMed
Summary

Hepatotoxicity of colchicinoids was assessed in rat liver cells. Only colchicinoids with a methylsulfonyl group at the C-10 position demonstrated significant liver damage, indicating a specific structural requirement for toxicity.

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Area of Science:

  • Pharmacology
  • Toxicology
  • Biochemistry

Context:

  • Hepatotoxicity is a significant concern in drug development.
  • Colchicinoids are a class of compounds with potential therapeutic and toxicological relevance.
  • Isolated rat hepatocytes provide a relevant in vitro model for studying drug-induced liver injury.

Purpose:

  • To evaluate the cytotoxicity of 32 colchicinoid compounds.
  • To identify structural features of colchicinoids associated with hepatotoxicity.
  • To correlate biochemical markers with observed cellular damage.

Summary:

  • Thirty-two colchicinoids were tested for their toxic effects on isolated rat hepatocytes.
  • Cytotoxicity was measured using biochemical markers including lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid peroxidation, and reduced glutathione (GSH) levels.

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  • A significant correlation was found between the presence of a methylsulfonyl group at the C-10 position and pronounced hepatotoxicity.

    • Impact:

    • Identifies a specific structural determinant (C-10 methylsulfonyl group) for colchicinoid-induced hepatotoxicity.
    • Provides valuable data for the risk assessment and potential drug design involving colchicinoid analogs.
    • Highlights the utility of isolated hepatocytes and specific biochemical markers for evaluating chemical toxicity.