Please use this identifier to cite or link to this item: https://doi.org/10.1177/1087057112447305
DC FieldValue
dc.titleAn investigation of the bioactivation potential and metabolism profile of zebrafish versus human
dc.contributor.authorChng, H.T.
dc.contributor.authorHo, H.K.
dc.contributor.authorYap, C.W.
dc.contributor.authorLam, S.H.
dc.contributor.authorChan, E.C.Y.
dc.date.accessioned2014-10-27T08:21:41Z
dc.date.available2014-10-27T08:21:41Z
dc.date.issued2012-08
dc.identifier.citationChng, H.T., Ho, H.K., Yap, C.W., Lam, S.H., Chan, E.C.Y. (2012-08). An investigation of the bioactivation potential and metabolism profile of zebrafish versus human. Journal of Biomolecular Screening 17 (7) : 974-986. ScholarBank@NUS Repository. https://doi.org/10.1177/1087057112447305
dc.identifier.issn10870571
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/100073
dc.description.abstractThe zebrafish model has been increasingly explored as an alternative model for toxicity screening of pharmaceutical drugs. However, little is understood about the bioactivation of drug to reactive metabolite and phase I and II metabolism of chemical in zebrafish as compared with human. The primary aim of our study was to establish the bioactivation potential of zebrafish using acetaminophen as a probe substrate. Our secondary aim was to perform metabolite profiling experiments on testosterone, a CYP3A probe substrate, in zebrafish and compare the metabolite profiles with that of human. The glutathione trapping assay of N-acetyl-p-benzoquinone imine demonstrated that zebrafish generates the same reactive metabolite as humans from the bioactivation of acetaminophen. Zebrafish possesses functional CYP3A4/5-like and UDP-glucuronosyltransferase metabolic activities on testosterone. Differential testosterone metabolism was observed among the two species. In silico docking studies suggested that the zebrafish CYP3A65 was responsible for the bioactivation of acetaminophen and phase I hydroxylation of testosterone. Our findings reinforce the need to further characterize the drug metabolism phenotype of zebrafish before the model can fully achieve its potential as an alternative toxicity screening model in drug research. © 2012 Society for Laboratory Automation and Screening.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1177/1087057112447305
dc.sourceScopus
dc.subjectacetaminophen
dc.subjectbioactivation
dc.subjectfish cytochrome P450
dc.subjectliver microsomes
dc.subjectphase II drug metabolism
dc.subjectreactive metabolites
dc.subjecttestosterone
dc.subjectzebrafish
dc.typeArticle
dc.contributor.departmentPHARMACY
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1177/1087057112447305
dc.description.sourcetitleJournal of Biomolecular Screening
dc.description.volume17
dc.description.issue7
dc.description.page974-986
dc.description.codenJBISF
dc.identifier.isiut000306324500012
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

41
checked on Jul 20, 2021

WEB OF SCIENCETM
Citations

37
checked on Jul 13, 2021

Page view(s)

126
checked on Jul 13, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.