Investigating the in vitro metabolism of veratridine: characterization of metabolites and involved cytochrome P450 isoforms.
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.
Ye
Xuan
X
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Wang
Yuguang
Y
Yang
Minghui
M
Wang
Qingqing
Q
Liang
Qiande
Q
Ma
Zengchun
Z
Zhang
Boli
B
Gao
Yue
Y
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D014701:Veratridine / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D014701:Veratridine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A