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Assessment of the inhibitory effects of pyrethroids against human carboxylesterases
Lei, Wei1,2; Wang, Dan-Dan2; Dou, Tong-Yi2; Hou, Jie3; Feng, Liang2; Yin, Heng2; Luo, Qun4; Sun, Jie1; Ge, Guang-Bo2; Yang, Ling2
KeywordPyrethroids Human Carboxylesterase 1 Deltamethrin Ligand-binding Sites
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
2017-04-15
ISSN0041-008X
DOI10.1016/j.taap.2017.02.018
Volume321Pages:48-56
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS KeywordHUMAN UDP-GLUCURONOSYLTRANSFERASES ; MAMMALIAN CARBOXYLESTERASES ; HYDROLYTIC METABOLISM ; LIQUID-CHROMATOGRAPHY ; CATALYTIC-PROPERTIES ; RISK-ASSESSMENT ; QUECHERS METHOD ; 1 CES1 ; ACTIVATION ; EXPOSURE
AbstractPyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC50 values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58 mu M, 2.39 mu M, and 33 mu M, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1. (C) 2017 Elsevier Inc. All rights reserved.
Language英语
WOS IDWOS:000397351900005
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Citation statistics
Cited Times:23[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/169293
Collection中国科学院大连化学物理研究所
Corresponding AuthorGe, Guang-Bo
Affiliation1.Dalian Med Univ, Affiliated Hosp 2, Dalian 110623, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
3.Dalian Med Univ, Dalian 116044, Peoples R China
4.Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Beijing 100080, Peoples R China
Recommended Citation
GB/T 7714
Lei, Wei,Wang, Dan-Dan,Dou, Tong-Yi,et al. Assessment of the inhibitory effects of pyrethroids against human carboxylesterases[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2017,321:48-56.
APA Lei, Wei.,Wang, Dan-Dan.,Dou, Tong-Yi.,Hou, Jie.,Feng, Liang.,...&Yang, Ling.(2017).Assessment of the inhibitory effects of pyrethroids against human carboxylesterases.TOXICOLOGY AND APPLIED PHARMACOLOGY,321,48-56.
MLA Lei, Wei,et al."Assessment of the inhibitory effects of pyrethroids against human carboxylesterases".TOXICOLOGY AND APPLIED PHARMACOLOGY 321(2017):48-56.
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