Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human

	Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human
	Ma, Xiao-Chi 1,2; Ning, Jing 1,2; Ge, Guang-Bo 1; Liang, Si-Cheng 1; Wang, Xiu-Li 1; Zhang, Bao-Jing 2; Huang, Shan-Shan 2; Li, Jing-Kui 2; Yang, Ling 1
刊名	drug metabolism and disposition
	2011-04-01
卷号	39 期号:4 页码:675-682
ISSN号	待补充
通讯作者	杨凌
产权排序	1,1
中文摘要	comparative metabolism of cinobufagin in liver microsomes from mouse, rat, dog, minipig, monkey, and human
英文摘要	cinobufagin (cb), a major bioactive component of the traditional chinese medicine chansu, has been reported to have potent antitumor activity. in this study, in vitro metabolism of cb among species was compared with respect to metabolic profiles, enzymes involved, and catalytic efficiency by using liver microsomes from human (hlm), mouse (mlm), rat (rlm), dog (dlm), minipig (plm), and monkey (cylm). significant species differences in cb metabolism were revealed. in particular, species-specific deacetylation and epimerization combined with hydroxylation existed in rlm, whereas hydroxylation was a major pathway in hlm, mlm, dlm, plm, and cylm. two monohydroxylated metabolites of cb in human and animal species were identified as 1 alpha-hydroxylcinobufagin and 5 beta-hydroxylcinobufagin by using liquid chromatography-mass spectrometry and two-dimensional nmr techniques. cyp3a4 was identified as the main isoform involved in cb hydroxylation in hlm on the basis of the chemical inhibition studies and screen assays with recombinant human cytochrome p450s. furthermore, ketoconazole, a specific inhibitor of cyp3a, strongly inhibited cb hydroxylation in mlm, dlm, plm, and cylm, indicating that cyp3a was responsible for cb hydroxylation in these animal species. the apparent substrate affinity and catalytic efficiency for 1 alpha- and 5 beta-hydroxylation of cb in liver microsomes from various species were also determined. plm appears to have km and total intrinsic clearance value (v(max)/k(m)) similar to those for hlm, and the total microsomal intrinsic clearance values for cb obeyed the following order: mouse > dog > monkey > human > minipig. these findings provide vital information to better understand the metabolic behaviors of cb among various species.
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy
关键词[WOS]	performance liquid-chromatography ; traditional chinese medicine ; human cytochrome-p450 3a4 ; toad venom ; in-vitro ; chan-su ; mass-spectrometry ; drug-metabolism ; bufadienolides ; inhibition
收录类别	SCI
语种	英语
WOS记录号	WOS:000288424400013
公开日期	2012-07-09
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/115812]
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.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 2.Dalian Med Univ, Sch Pharmaceut Sci, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Ma, Xiao-Chi,Ning, Jing,Ge, Guang-Bo,et al. Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human[J]. drug metabolism and disposition,2011,39(4):675-682.
APA	Ma, Xiao-Chi.,Ning, Jing.,Ge, Guang-Bo.,Liang, Si-Cheng.,Wang, Xiu-Li.,...&Yang, Ling.(2011).Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human.drug metabolism and disposition,39(4),675-682.
MLA	Ma, Xiao-Chi,et al."Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human".drug metabolism and disposition 39.4(2011):675-682.