Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids

	Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids
	He, Yu-Qi 1; Yang, Li 1; Liu, Hui-Xin 2; Zhang, Jiang-Wei 2; Liu, Yong 2; Fong, Alan 3; Xiong, Ai-Zhen 1; Lu, Yan-Liu 1; Yang, Ling 2; Wang, Chang-Hong 1
刊名	chemical research in toxicology
	2010-03-01
卷号	23 期号:3 页码:591-599
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.
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
关键词[WOS]	human udp-glucuronosyltransferases ; messenger-rna expression ; human liver-microsomes ; species-differences ; n-glucuronidation ; rat ; monocrotaline ; activation ; plants
收录类别	SCI
语种	英语
WOS记录号	WOS:000275411700020
公开日期	2015-11-17
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/141648]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
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
推荐引用方式 GB/T 7714	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.
APA	He, Yu-Qi.,Yang, Li.,Liu, Hui-Xin.,Zhang, Jiang-Wei.,Liu, Yong.,...&Wang, Zheng-Tao.(2010).Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids.chemical research in toxicology,23(3),591-599.
MLA	He, Yu-Qi,et al."Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids".chemical research in toxicology 23.3(2010):591-599.