title: In vitro metabolism of the cyanotoxin cylindrospermopsin in HepaRG cells and liver tissue fractions.
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.
authors.affiliation: ANSES, French Agency for Food, Environmental and Occupational Health Safety, Fougères Laboratory, 10B rue Claude Bourgelat - Javené, CS 40608, 35306, Fougères Cedex, France; Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Straße 11, 12489, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kittler
authors.affiliation: ANSES, French Agency for Food, Environmental and Occupational Health Safety, Fougères Laboratory, 10B rue Claude Bourgelat - Javené, CS 40608, 35306, Fougères Cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Hurtaud-Pessel
authors.affiliation: Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Straße 11, 12489, Berlin, Germany; Leibniz-Institute of Vegetable and Ornamental Crops Großbeeren/Erfurt e.V., Theodor-Echtermeyer-Weg 1, 14979, Großbeeren, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Maul
authors.affiliation: Federal Institute for Risk Assessment (BfR), Max-Dohrn-Straße 8-10, 10589, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Kolrep
authors.affiliation: ANSES, French Agency for Food, Environmental and Occupational Health Safety, Fougères Laboratory, 10B rue Claude Bourgelat - Javené, CS 40608, 35306, Fougères Cedex, France. Electronic address: valerie.fessard@anses.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
mesh_terms: D000470:Alkaloids; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria / Q000737:chemistry*; D000087522:Cyanobacteria Toxins; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D007700:Kinetics; D013058:Mass Spectrometry; D050216:Metabolic Detoxication, Phase I; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D053719:Tandem Mass Spectrometry; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity
chemical_list: D000470:Alkaloids; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D065692:Cytochrome P-450 CYP3A Inhibitors; C089595:cylindrospermopsin; D014498:Uracil; D007654:Ketoconazole
keywords: Cylindrospermopsin; HepaRG cells; LC-HRMS; Liver tissue fractions; Metabolism; Quantification