In vitro metabolism of the cyanotoxin cylindrospermopsin in HepaRG cells and liver tissue fractions

Toxicon. 2016 Feb;110:47-50. doi: 10.1016/j.toxicon.2015.11.007. Epub 2015 Dec 2.

Abstract

No evidence for phase I metabolites of the cyanotoxin cylindrospermopsin (CYN) was given using HepaRG cells and different liver tissue fractions when studying metabolic conversion. Although the application of ketoconazole, a CYP3A4 inhibitor, led to a decreased cytotoxicity of CYN, no metabolites were detected applying high resolution mass spectrometry. Quantification of non-modified CYN led to recovery rates of almost 100%. Consequently, reduction of CYN toxicity in the presence of metabolism inhibiting agents must be attributed to alternative pathways.

Keywords: Cylindrospermopsin; HepaRG cells; LC-HRMS; Liver tissue fractions; Metabolism; Quantification.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Animals
  • Bacterial Toxins / metabolism*
  • Bacterial Toxins / toxicity
  • Biotransformation / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Cyanobacteria / chemistry*
  • Cytochrome P-450 CYP3A Inhibitors / pharmacology
  • Cytosol / drug effects
  • Cytosol / enzymology
  • Cytosol / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism*
  • Humans
  • Ketoconazole / pharmacology
  • Kinetics
  • Mass Spectrometry
  • Metabolic Detoxication, Phase I
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Rats
  • Tandem Mass Spectrometry
  • Uracil / analogs & derivatives*
  • Uracil / metabolism
  • Uracil / toxicity

Substances

  • Alkaloids
  • Bacterial Toxins
  • Cytochrome P-450 CYP3A Inhibitors
  • cylindrospermopsin
  • Uracil
  • Ketoconazole