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The cyclooxigenase-2 Inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observations

dc.contributor.authorFerreira, Tiago
dc.contributor.authorCampos, Sandra
dc.contributor.authorSilva, Mónica G.
dc.contributor.authorRibeiro, Rita
dc.contributor.authorSantos, Susana
dc.contributor.authorAlmeida, José
dc.contributor.authorPires, Maria João
dc.contributor.authorCosta, Rui Miguel G. da
dc.contributor.authorMarcos, Cláudia Córdova
dc.contributor.authorNogueira, António
dc.contributor.authorNeuparth, Maria João
dc.contributor.authorMedeiros, Rui
dc.contributor.authorBastos, Margarida Maria da Silva Monteiro
dc.contributor.authorGaivão, Isabel
dc.contributor.authorPeixoto, Francisco
dc.contributor.authorOliveira, Maria Manuel
dc.contributor.authorOliveira, Paula Alexandra
dc.date.accessioned2020-11-24T10:47:14Z
dc.date.available2020-11-24T10:47:14Z
dc.date.issued2019
dc.description.abstractCarcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16-/-, n = 10, parecoxib-treated); II (HPV16-/-n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/-, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn't modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFerreira, TIago [et al.] (2019) - The cyclooxigenase-2 Inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observations. International Journal of Molecular Sciences. ISSN 1422-0067. Vol. 20, nº 16, p. 3902. DOI: 10.3390/ijms20163902pt_PT
dc.identifier.doi10.3390/ijms20163902pt_PT
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.11/7312
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationCentre for the Research and Technology of Agro-Environmental and Biological Sciences
dc.relationAnimal and Veterinary Research Centre
dc.relationLaboratory for Process Engineering, Environment, Biotechnology and Energy
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/20/16/3902pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAnimalspt_PT
dc.subjectAnticarcinogenic agentspt_PT
dc.subjectCyclooxygenase 2 Inhibitorspt_PT
dc.subjectFemalept_PT
dc.subjectHuman papillomavirus 16pt_PT
dc.subjectIsoxazolespt_PT
dc.subjectMicept_PT
dc.subjectMice transgenicpt_PT
dc.subjectPapillomavirus infectionspt_PT
dc.subjectSkinpt_PT
dc.subjectSkin neoplasmspt_PT
dc.titleThe cyclooxigenase-2 Inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observationspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for the Research and Technology of Agro-Environmental and Biological Sciences
oaire.awardTitleAnimal and Veterinary Research Centre
oaire.awardTitleLaboratory for Process Engineering, Environment, Biotechnology and Energy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FAGR%2F04033%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FCVT%2F00772%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FEQU%2F00511%2F2019/PT
oaire.citation.issue16pt_PT
oaire.citation.startPage3902pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume20pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameC´órdova Marcos
person.givenNameCláudia
person.identifier.ciencia-id8014-8F33-74AF
person.identifier.orcid0000-0002-2108-2629
person.identifier.scopus-author-id55259775600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery7241ff3f-7c4f-4688-b938-5dae4ca343dd
relation.isProjectOfPublicationa1c8f4ed-798a-4f38-a212-2cc672273412
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relation.isProjectOfPublication.latestForDiscoverya1c8f4ed-798a-4f38-a212-2cc672273412

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