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dc.contributor.authorZloh, Mire
dc.contributor.authorPerez Diaz, Noelia
dc.contributor.authorTang, Leslie
dc.contributor.authorPatel, Pryank
dc.contributor.authorMacKenzie, Louise Susan
dc.date.accessioned2016-04-04T11:44:07Z
dc.date.available2016-04-04T11:44:07Z
dc.date.issued2016-02-01
dc.identifier.citationZloh , M , Perez Diaz , N , Tang , L , Patel , P & MacKenzie , L S 2016 , ' Evidence that Diclofenac and Celecoxib are thyroid hormone receptor beta antagonists ' , Life Sciences , vol. 146 , pp. 66-72 . https://doi.org/10.1016/j.lfs.2016.01.013
dc.identifier.issn0024-3205
dc.identifier.otherPURE: 9879531
dc.identifier.otherPURE UUID: 315771ad-79f5-4646-a4ea-bf98d1eff294
dc.identifier.otherPubMed: 26792060
dc.identifier.otherScopus: 84954286207
dc.identifier.urihttp://hdl.handle.net/2299/16907
dc.descriptionThis document is the Accepted Manuscript version, made available under the terms of of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
dc.description.abstractLong term use of NSAIDs is linked to side effects such as gastric bleeding and myocardial infarction. AIMS: Use of in silico methods and pharmacology to investigate the potential for NSAIDs diclofenac, celecoxib and naproxen to bind to nuclear receptors. MATERIALS AND METHODS: In silico screening predicted that both diclofenac and celecoxib has the potential to bind to a number of different nuclear receptors; docking analysis confirmed a theoretical ability for diclofenac and celecoxib but not naproxen to bind to TRβ. KEY FINDINGS: Results from TRβ luciferase reporter assays confirmed that both diclofenac and celecoxib display TRβ antagonistic properties; celecoxib, IC50 3.6×10(-6)M, and diclofenac IC50 5.3×10(-6)M, comparable to the TRβ antagonist MLS (IC50 3.1×10(-6)M). In contrast naproxen, a cardio-sparing NSAID, lacked TRβ antagonist effects. In order to determine the effects of NSAIDs in whole organ in vitro, we used isometric wire myography to measure the changes to Triiodothyronine (T3) induced vasodilation of rat mesenteric arteries. Incubation of arteries in the presence of the TRβ antagonist MLS000389544 (10(-5)M), as well as diclofenac (10(-5)M) and celecoxib (10(-5)M) but not naproxen significantly inhibited T3 induced vasodilation compared to controls. SIGNIFICANCE: These results highlight the benefits of computational chemistry methods used to retrospectively analyse well known drugs for side effects. Using in silico and in vitro methods we have shown that both celecoxib and diclofenac but not naproxen exhibit off-target TRβ antagonist behaviour, which may be linked to their detrimental side effectsen
dc.language.isoeng
dc.relation.ispartofLife Sciences
dc.rights/dk/atira/pure/core/openaccesspermission/embargoed
dc.titleEvidence that Diclofenac and Celecoxib are thyroid hormone receptor beta antagonistsen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.contributor.institutionCentre for Hazard Detection and Protection Research
dc.contributor.institutionDepartment of Pharmacy, Pharmacology and Postgraduate Medicine
dc.contributor.institutionBiochemistry and Bioinformatics
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionDiabetic neuropathies
dc.contributor.institutionBasic and Clinical Science Unit
dc.contributor.institutionPsychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
dc.date.embargoedUntil2017-01-11
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Accepted Version
dcterms.dateAccepted2016-01-09
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.lfs.2016.01.013
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2017-01-11Z
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.date.embargo2017-01-11Z
herts.rights.accesstypeopenAccess


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