Ma_2017_Toxicol.In.Vitro_44_280

Reference

Title : Comparative metabolism of DDAO benzoate in liver microsomes from various species - Ma_2017_Toxicol.In.Vitro_44_280
Author(s) : Ma HY , Yang JD , Hou J , Zou LW , Jin Q , Hao DC , Ning J , Ge GB , Yang L
Ref : Toxicol In Vitro , 44 :280 , 2017
Abstract :

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 approximately PLM>RLM>HLM approximately 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.

PubMedSearch : Ma_2017_Toxicol.In.Vitro_44_280
PubMedID: 28647665

Related information

Inhibitor Loperamide
Substrate DDAB

Citations formats

Ma HY, Yang JD, Hou J, Zou LW, Jin Q, Hao DC, Ning J, Ge GB, Yang L (2017)
Comparative metabolism of DDAO benzoate in liver microsomes from various species
Toxicol In Vitro 44 :280

Ma HY, Yang JD, Hou J, Zou LW, Jin Q, Hao DC, Ning J, Ge GB, Yang L (2017)
Toxicol In Vitro 44 :280