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学科主题: 物理化学
题名: Cytochrome P450-based toxicity research of Pyrrolizidine alkaloids
作者: He YQ(何芋岐) ;  Liu Y(刘勇) ;  Yang L(杨丽) ;  Zhang JW(张江伟) ;  Wang ZT(王峥涛) ;  Yang L(杨凌)
会议名称: 第三届中日双边药理学和临床药理学会议
会议日期: 2007-8-23
出版日期: 2007-08-23
会议地点: 中国
通讯作者: 杨凌
部门归属: 十八室
主办者: 中国药理学会
摘要: Pyrrolizidine alkaloids were considered as the essential components in the toxicity of some composite plants. The previous study suggested that cytochrome P450 (CYPs)–mediated bioactivation and succedent formation of DNA adducts triggered toxicity of pyrrolizidine alkaloids including Clivorine and Riddline, such as genotoxicity and mutagenesis. However, there is little knowledge about the metabolism properties of Adonifoline, another pyrrolizidine alkaloid in the plant of Seneciea scandens, and there is little knowledge about the influence to CYPs activity directly or indirectly by pyrrolizidine alkaloids used in previous study. The purpose was to study the metabolism properties of several pyrrolizidine alkaloids including Adonifoline, Monocrotaline, Isoline, Clivorine and Senecionine, as well as their potential of CYPs-mediated bioactivation. METHODS A classical in vitro human microsomes incubation system was used in this study, and experiments included: 1) Assay of metabolism of Adonifoline, the major pyrrolizidine alkaloid in the plant of Seneciea scandens; 2) Assay of inhibitory effects against CYPs acticities by Adonifoline, Monocrotaline, Isoline, Clivorine and Senecionine; 3) Assay of time-dependent and NADPH-dependent inhibition of CYPs activities by Adonfioline, Monocrotaline, Isoline, Clivorine and Senecionine. RESULTS One metabolite, that is Adonifoline N-oxide, of Adonifoline was identified by LC-MS. Adonifoline, Monocrotaline, Isoline, Clivorine and Senecionine showed no inhibitory effects against tested CYPs activities including CYP3A4, CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP2C8 and CYP2C9 at a high concentration of 100 μM; and there were also no time-dependent and NADPH-dependent inhibition against CYPs described above found. CONCLUSION A N-oxide metabolite of Adonifoline was identified. In addition, the tested pyrrolizidine alkaloids have no inhibitory effects against tested CYPs activities, and also no CYPs-mediated bioactivation found. Key words: pyrrolizidine alkaloids; cytochrome P450;bioactivation; inhibition
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/112722
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:
He YQ,Liu Y,Yang L,et al. Cytochrome P450-based toxicity research of Pyrrolizidine alkaloids[C]. 见:第三届中日双边药理学和临床药理学会议. 中国. 2007-8-23.
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