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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids
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Animals
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Bacterial Toxins / metabolism*
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Bacterial Toxins / toxicity
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Biotransformation / drug effects
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Cell Line
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Cell Survival / drug effects
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Chromatography, High Pressure Liquid
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Cyanobacteria / chemistry*
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Cyanobacteria Toxins
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Cytochrome P-450 CYP3A Inhibitors / pharmacology
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Cytosol / drug effects
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Cytosol / enzymology
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Cytosol / metabolism
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Hepatocytes / drug effects
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Hepatocytes / enzymology
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Hepatocytes / metabolism*
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Humans
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Ketoconazole / pharmacology
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Kinetics
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Mass Spectrometry
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Metabolic Detoxication, Phase I
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Microsomes, Liver / drug effects
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Microsomes, Liver / enzymology
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Microsomes, Liver / metabolism
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Rats
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Tandem Mass Spectrometry
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Uracil / analogs & derivatives*
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Uracil / metabolism
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Uracil / toxicity
Substances
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Alkaloids
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Bacterial Toxins
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Cyanobacteria Toxins
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Cytochrome P-450 CYP3A Inhibitors
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cylindrospermopsin
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Uracil
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Ketoconazole