Investigating the in vitro metabolism of veratridine: characterization of metabolites and involved cytochrome P450 isoforms.
J Chromatogr B Analyt Technol Biomed Life Sci
; 877(3): 141-8, 2009 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-19097948
ABSTRACT
Veratridine is a lipid-soluble alkaloid extracted from Veratrum officinale and other species of the family Liliaceae. Veratridine prevents inactivation of Na(+) channel via binding the receptor site 2, causes influx of sodium ion and depolarization and induces apoptosis of neuronal cells. In the present study, we investigated the metabolism of veratridine and the effects of selective cytochrome P450 (CYP) inhibitors on the metabolism of veratridine in rat liver microsomes. The metabolites were separated and assayed by liquid-chromatography-electrospray ionization-ion trap tandem mass spectrometry (LC-ESI-QIT-MSn), and further identified by their mass spectra and chromatographic behaviors. Result showed that four CYP isoforms (CYP1A, CYP2B, CYP2E1, CYP3A) were involved in the metabolism of veratridine in vitro and seven metabolites of veratridine were detected incubating with rat liver microsomes. Some of the metabolites were presumed to be potential mediates of neurotoxicity via protein binging. Further research in vivo needs to link the metabolism of veratridine to its toxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Veratridina
/
Sistema Enzimático del Citocromo P-450
Límite:
Animals
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
China