期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 105, 期 -, 页码 506-517出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2017.04.041
关键词
Enniatin B1; Hepatic biotransformation; In vitro; In vivo; Metabolites; Pig
资金
- FUNtox, a strategic program on Fungi and Mycotoxins in a One Health perspective of the Norwegian Veterinary Institute
Enniatins (ENNs) are hexadepsipeptidic mycotoxins produced by Fusarium species. They occur in mg/kg levels in grain from Northern climate areas. Major ENNs such as ENN B and Bl have shown considerable cytotoxicity in different in vitro test systems. To adequately assess exposure and in vivo toxicity the toxicokinetic properties need to be investigated. The present study describes the metabolism of ENN B1 both in vitro and in vivo in pigs, comparing metabolites found in vitro in experiments with liver microsomes from different pig strains to those found in the plasma of pigs after single oral or intravenous application of ENN Bl. Metabolites of hepatic biotransformation were tentatively identified and characterised by high performance liquid chromatography coupled to ion trap and high-resolution mass spectrometry, as well as chemical derivatisations. Kinetic parameters of metabolite formation and elimination were determined. Metabolite formation was higher when ENN Bl was absorbed from the gut compared to intravenous administration indicating pre-systemic metabolism of ENN B1 after oral uptake. The in vitro approach resulted in the detection of ten ENN B1 metabolites, while six were detected in in vivo samples. The putative ENN B1 metabolites were products of hydroxylation, carbonylation, carboxylation and oxidative demethylation reactions. (C) 2017 Published by Elsevier Ltd.
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