Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

Metabolism study of veratramine associated with neurotoxicity by using HPLC–MSn

Language

English

Abstract

© 2014 The Author. Published by Oxford University Press. All rights reserved. Veratramine (VAM) is the major lipid-soluble alkaloid existing in Veratrum nigrum L. that has been demonstrated to exert neurotoxic effects. To better understand the potential mechanism of neurotoxicity of VAM, VAM-induced DNA damage was measured in the cerebellum and cerebral cortex of mice after a 7-day repetitive oral dose by using single-cell gel electrophoresis (comet assay). A method based on high-performance liquid chromatography-electrospray ionization tandem mass spectrometry was developed for the determination of VAM and its in vivo and in vitro metabolites, to establish the potential correlation between metabolites and neurotoxicity. In vitro experiment was carried out using rat liver microsomes, whereas the in vivo study was conducted on rats at a single dose of 3 mg/kg. The results showed that VAM caused DNA damage in the cerebellum and cerebral cortex of mice in a dose-dependent manner. Phenyl mono-oxidation, sulfate conjugation and phenyl di-oxidation were proposed to be the main in vivo metabolic pathways of VAM, whereas the major in vitro metabolic pathways were phenyl mono-oxidation, hydroxylation and methylation. Phenyl-oxidation reaction was likely to be associated with reactive oxygen species production, leading to the DNA damage in the mouse brain.

Publication Date

2015

Source Publication Title

Journal of Chromatographic Science

Volume

53

Issue

7

Start Page

1092

End Page

1099

Publisher

Oxford University Press

DOI

10.1093/chromsci/bmu171

Link to Publisher's Edition

http://dx.doi.org/10.1093/chromsci/bmu171

ISSN (print)

00219665

ISSN (electronic)

1945239X

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