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

• Application of multiple in vitro methods for metabolism studies on CYN.
• No evidence for CYN phase I metabolites.
• Ketoconazole is protective against CYN toxicity in vitro.

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.