DICP OpenIR
学科主题物理化学
Characterization of in vitro bioactivation of rutaecarpine in human liver microsomes (HLMs)
Fang ZZ(房中则); Yang L(杨凌); Ling Yang
会议名称9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics
会议日期2010-9-4
2010-09-04
会议地点土耳其
页码79/2
部门归属十八室
主办者国际药物代谢学会
英文摘要Reactive drug metabolites have been always considered mediators of drug-induced toxicities and risk would increase with the increasing reactive metabolites. Rutaecarpine is a main alkaloid isolated from Evodia rutaecarpa (Wu-chu-yu), which has been used as a herbal medicine for the treatment of gastrointestinal disorder and headache. Previous reports have demonstrated that rutaecarpine mainly underwent cytochrome P450 (CYP)-mediated oxidative metabolism. Of significant interest in many biotransformation is the detection and characterization of 3-hydroxyrutaecarpine which might undergo a two-electron oxidation leading to formation of an electrophilic quinine imine intermediate. To test these hypotheses, we examined the bioactivation potential of rutaecarpine in human liver microsomes (HLMs) and recombinant CYP isoforms. LC-MS/MS analysis of extracts of human liver microsomal incubations containing rutaecarpine (200 μM), NADPH and GSH revealed the addition of a glutathionyl moiety to the 3-hydroxyl metabolite of ruteacarpine. Among tested recombinant CYP isoforms, CYP3A4 had the highest activity to catalyze the bioactivation of rutaecarpine. CYP1A2 and CYP2D6 also catalyzed the formation of GSH adduct of ruteacarpine. Previous studies showed that ruteacarpine exhibit mechanism-based inhibition towards CYP3A4 (Iwata et al., 2005). Ruteacarpine-induced immunosuppression was proposed to be associated with its bioactivation (Jeon et al., 2006). The present results might provide a potential explanation for these two phenomena.
语种中文
WOS记录号WOS:000281147700140
引用统计
文献类型会议论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/114332
专题中国科学院大连化学物理研究所
通讯作者Ling Yang
推荐引用方式
GB/T 7714
Fang ZZ,Yang L,Ling Yang. Characterization of in vitro bioactivation of rutaecarpine in human liver microsomes (HLMs)[C],2010:79/2.
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