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

Yue Cong, Jinggong Guo, Zhi Tang, Shuhai LIN, Qingchun Zhang, Jing Li, Zongwei CAI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1092-1099
Number of pages8
JournalJournal of Chromatographic Science
Volume53
Issue number7
DOIs
Publication statusPublished - Aug 2015

Scopus Subject Areas

  • Analytical Chemistry

Fingerprint

Dive into the research topics of 'Metabolism study of veratramine associated with neurotoxicity by using HPLC-MS<sup>n</sup>'. Together they form a unique fingerprint.

Cite this