Comparative metabolism of DDAO benzoate in liver microsomes from various species

	Comparative metabolism of DDAO benzoate in liver microsomes from various species
	Ge, Guang-Bo 1,2; Ma, Hong-Ying 1,4; Yang, Jia-Da 5; Hou, Jie 3; Zou, Li-Wei ; Jin, Qiang 2; Hao, Da-Cheng 4; Ning, Jing 1,3; Yang, Ling 2
刊名	TOXICOLOGY IN VITRO
	2017-10-01
卷号	44 页码:280-286
关键词	DDAB hydrolysis Carboxylesterase 2 (CE2) Species differences Liver microsomes
英文摘要	DDAB (6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate) is a newly developed near-infrared fluorescent probe for human carboxylesterase 2 (hCE2), exhibiting high specificity and good reactivity for real-time monitoring the enzymatic activities of hCE2 in complex biological systems. In order to explore the applicability of DDAB in commonly used animal species, the interspecies difference in DDAB hydrolysis was carefully investigated by using liver microsomes from human and five experimental animals including mouse, rat, dog, minipig and monkey. Metabolite profiling demonstrated that DDAB hydrolysis could be catalyzed by all tested liver microsomes from different animals but displayed significant difference in the reaction rate. Chemical inhibition assays demonstrated that carboxylesterases (CEs) were the major enzymes involved in DDAB hydrolysis in all tested liver microsomes, indicating that DDAB was a selective substrate of CEs in a variety of mammals. However, the differential effects of loperamide (LPA, a specific inhibitor against hCE2) on DDAB hydrolysis among various species were observed. The apparent kinetic parameters and the maximum intrinsic clearances (CLmax) for DDAB hydrolysis in liver microsomes from different animals were determined, and the order of CLmax values for the formation of DDAO was CyLM > MLM approximate to PLM > RLM > HLM approximate to DLM. These findings were helpful for the rational use of DDAB as an imaging tool for CE2 in different mammals, as well as for translational researches on the function of mammalian CEs and CE2-associated drug-drug interactions.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Toxicology
研究领域[WOS]	Toxicology
关键词[WOS]	HUMAN CARBOXYLESTERASE 2 ; HUMAN INTESTINAL CARBOXYLESTERASE ; SUBSTRATE-SPECIFICITY ; SELECTIVE INHIBITORS ; DRUG-METABOLISM ; HYDROLYSIS ; PRODRUG ; RAT ; ACTIVATION ; IRINOTECAN
收录类别	SCI
语种	英语
WOS记录号	WOS:000409395000033
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/149911]
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, Dalian 116023, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Shanghai 201210, Peoples R China 3.Dalian Med Univ, Dalian 116044, Peoples R China 4.Dalian Jiaotong Univ, Sch Environm & Chem Engn, Biotechnol Inst, Dalian 116028, Peoples R China 5.Kaili Univ, Sch Environm & Life Sci, Kaili 556011, Peoples R China
推荐引用方式 GB/T 7714	Ge, Guang-Bo,Ma, Hong-Ying,Yang, Jia-Da,et al. Comparative metabolism of DDAO benzoate in liver microsomes from various species[J]. TOXICOLOGY IN VITRO,2017,44:280-286.
APA	Ge, Guang-Bo.,Ma, Hong-Ying.,Yang, Jia-Da.,Hou, Jie.,Zou, Li-Wei.,...&Yang, Ling.(2017).Comparative metabolism of DDAO benzoate in liver microsomes from various species.TOXICOLOGY IN VITRO,44,280-286.
MLA	Ge, Guang-Bo,et al."Comparative metabolism of DDAO benzoate in liver microsomes from various species".TOXICOLOGY IN VITRO 44(2017):280-286.