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题名: Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids
作者: He, Yu-Qi1;  Yang, Li1;  Liu, Hui-Xin2;  Zhang, Jiang-Wei2;  Liu, Yong2;  Fong, Alan3;  Xiong, Ai-Zhen1;  Lu, Yan-Liu1;  Yang, Ling2;  Wang, Chang-Hong1;  Wang, Zheng-Tao1
刊名: CHEMICAL RESEARCH IN TOXICOLOGY
发表日期: 2010-03-01
DOI: 10.1021/tx900328f
卷: 23, 期:3, 页:591-599
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine ;  Physical Sciences
类目[WOS]: Chemistry, Medicinal ;  Chemistry, Multidisciplinary ;  Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ;  Chemistry ;  Toxicology
英文摘要: Pyrrolizidine alkaloids (PAS) possess significant hepatotoxicity to humans and animals after metabolic activation by liver P450 enzymes. Metabolism pathways of PAs have been studied for several decades, including metabolic activation, hydroxylation, N-oxidation, and hydrolysis. However, the glucuronidation of intact PAs has not been investigated, although glucuronidation plays an important role in the elimination and detoxication of xenobiotics. In this study, PAs glucuronidation was investigated, and three important points were found. First, we demonstrated that senecionine (SEN)-a representative hepatotoxic PA-could be conjugated by glucuronic acid via an N-glucuronidation reaction catalyzed by uridine diphosphate glucuronosyl transferase in human liver microsomes. Second, glucuronidation of SEN was catalyzed not only by human but also other animal species and showed significant species differences. Rabbits, cattle, sheep, pigs. and humans showed the significantly higher glucuronidation activity than mice. rats, dogs, and guinea pigs on SEN. Kinetics of SEN glucuronidation in humans, pigs, and rabbits followed the one-site binding model of the Michaelis-Menten equation, while cattle and sheep followed the two-sites binding model of the Michaelis-Menten equation. Third, besides SEN, other hepatotoxic PAs including monocrotaline, adonifoline, and isoline also underwent N-glucuronidation in humans and several animal species such as rabbits, cattle, sheep, and pigs.
关键词[WOS]: HUMAN UDP-GLUCURONOSYLTRANSFERASES ;  MESSENGER-RNA EXPRESSION ;  HUMAN LIVER-MICROSOMES ;  SPECIES-DIFFERENCES ;  N-GLUCURONIDATION ;  RAT ;  MONOCROTALINE ;  ACTIVATION ;  PLANTS
语种: 英语
WOS记录号: WOS:000275411700020
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/141648
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Shanghai Univ Tradit Chinese Med, MOE Key Lab Standardizat Chinese Med, Inst Chinese Mat Med, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
3.Sarawak Gen Hosp, Clin Res Ctr, Kuching 93000, Malaysia

Recommended Citation:
He, Yu-Qi,Yang, Li,Liu, Hui-Xin,et al. Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2010,23(3):591-599.
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