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Comparative metabolism of DDAO benzoate in liver microsomes from various species
Ma, Hong-Ying1,2; Yang, Jia-Da3; Hou, Jie4; Zou, Li-Wei; Jin, Qiang5; Hao, Da-Cheng1; Ning, Jing2,4; Ge, Guang-Bo2,5; Yang, Ling5
KeywordDdab Hydrolysis Carboxylesterase 2 (Ce2) Species Differences Liver Microsomes
Source PublicationTOXICOLOGY IN VITRO
2017-10-01
DOI10.1016/j.tiv.2017.06.020
Volume44Pages:280-286
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectToxicology
WOS Research AreaToxicology
WOS KeywordHUMAN CARBOXYLESTERASE 2 ; HUMAN INTESTINAL CARBOXYLESTERASE ; SUBSTRATE-SPECIFICITY ; SELECTIVE INHIBITORS ; DRUG-METABOLISM ; HYDROLYSIS ; PRODRUG ; RAT ; ACTIVATION ; IRINOTECAN
AbstractDDAB (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.
Language英语
WOS IDWOS:000409395000033
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/149911
Collection中国科学院大连化学物理研究所
Affiliation1.Dalian Jiaotong Univ, Sch Environm & Chem Engn, Biotechnol Inst, Dalian 116028, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
3.Kaili Univ, Sch Environm & Life Sci, Kaili 556011, Peoples R China
4.Dalian Med Univ, Dalian 116044, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Shanghai 201210, Peoples R China
Recommended Citation
GB/T 7714
Ma, Hong-Ying,Yang, Jia-Da,Hou, Jie,et al. Comparative metabolism of DDAO benzoate in liver microsomes from various species[J]. TOXICOLOGY IN VITRO,2017,44:280-286.
APA Ma, Hong-Ying.,Yang, Jia-Da.,Hou, Jie.,Zou, Li-Wei.,Jin, Qiang.,...&Yang, Ling.(2017).Comparative metabolism of DDAO benzoate in liver microsomes from various species.TOXICOLOGY IN VITRO,44,280-286.
MLA Ma, Hong-Ying,et al."Comparative metabolism of DDAO benzoate in liver microsomes from various species".TOXICOLOGY IN VITRO 44(2017):280-286.
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