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学科主题: 物理化学
题名: Characterization of in vitro bioactivation of rutaecarpine in human liver microsomes (HLMs)
作者: Fang ZZ(房中则) ;  Yang L(杨凌)
会议名称: 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics
会议日期: 2010-9-4
出版日期: 2010-09-04
会议地点: 土耳其
通讯作者: Ling Yang
部门归属: 十八室
主办者: 国际药物代谢学会
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
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内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/114332
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Fang ZZ,Yang L. Characterization of in vitro bioactivation of rutaecarpine in human liver microsomes (HLMs)[C]. 见:9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics. 土耳其. 2010-9-4.
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