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学科主题: 物理化学
题名: Metabolic Activation of Strychnine to Reactive Intermediates by Human Liver Microsomes and CYP3A4
作者: Mao YX(毛玉玺) ;  Fang ZZ(房中则) ;  Ge GB(葛广波) ;  Yang L(杨凌)
会议名称: 9th International Meeting of the International Society for the Study of Xenobiotics in Istanbul
会议日期: 2010-9-4
出版日期: 2010-09-04
会议地点: 土耳其
其他题名: 士的宁在人肝微粒体和CYP3A4中生物激活产生活性中间体
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: Strychnine is one of the main active components of Semen Strychni which has been used as a traditional Chinese medicine for the treatment of nervous diseases, vomiting and arthritic and traumatic pains. It is highly toxic to humans and most domestic animals and acts as the poison curare originating from South America. Chemically reactive metabolites may induce toxicities and adverse side reactions, which might lead to withdrawing of the drug from market. There is exiting metabolic pathways in which Strychnine is oxidized to hydroxyl metabolites which might undergo a two-electron oxidation leading to formation of an electrophilic quinine imine intermediate. It is of significant interest to detect and characterization of reactive intermediates generated in the disposition of strychnine. Bioactivation potential of strychnine in human liver microsomes and recombinant CYP isoforms were performed. LC-MS/MS analysis of extracts of human liver microsomal incubations containing strychnine (200 μM), NADPH and GSH revealed a GSH adduct of the metabolite of strychnine was detected. Among tested recombinant CYP isoforms, CYP3A4 had the highest activity to catalyze the bioactivation of strychnine. Selective chemical inhibition investigation demostrated that ketoconazole dramatically inhibited the formation of GSH adduct. In the further stage of this investigation, GSH adduct is to be chemically synthesized to examine whether strychnine or GSH adduct plays a role in the toxicity of strychnine.
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/321008/114322
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:
Mao YX,Fang ZZ,Ge GB,et al. Metabolic Activation of Strychnine to Reactive Intermediates by Human Liver Microsomes and CYP3A4[C]. 见:9th International Meeting of the International Society for the Study of Xenobiotics in Istanbul. 土耳其. 2010-9-4.
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