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

2019Journal article Open access
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dc.contributor.authorFerreira, Tiago
dc.contributor.authorCampos, Sandra
dc.contributor.authorSilva, Mónica
dc.contributor.authorRibeiro, Rita
dc.contributor.authorSantos, Susana
dc.contributor.authorAlmeida, José L.S.
dc.contributor.authorPires, Maria João
dc.contributor.authorCosta, Rui Miguel Gil
dc.contributor.authorCórdova, Cláudia
dc.contributor.authorNogueira, António José M.
dc.contributor.authorNeuparth, Maria João
dc.contributor.authorMedeiros, Rui
dc.contributor.authorBastos, Margarida M.S.M.
dc.contributor.authorGaivão, Isabel
dc.contributor.authorPeixoto, Francisco P.
dc.contributor.authorOliveira, Maria Manuel
dc.contributor.authorOliveira, Paula A.
dc.date.accessioned2018-02-19T10:00:00Z
dc.date.accessioned2020-01-06T14:10:24Z
dc.date.available2018-01-19T10:00:00Z
dc.date.available2020-01-06T14:10:24Z
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 e cacy, but also considerable toxicity. This study addresses the chemopreventive e ect 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 e ects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.
dc.description.sponsorshipThis work is supported by National Funds by FCT—Portuguese Foundation for Science and Technology, under the projects UID/AGR/04033/2019, UID/CVT/00772/2019 and UID/EQU/00511/2019 - Laboratory for Process Engineering, Environment, Biotechnology and Energy—LEPABE funded by national funds through FCT/MCTES (PIDDAC); Project “LEPABE-2-ECO-INNOVATION”—NORTE-01-0145-FEDER-000005, funded by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund.
dc.description.versioninfo:eu-repo/semantics/publishedVersionen_EN
dc.identifier.citationFerreira, Tiago; Campos, Sandra; Silva, Mónica G.; Ribeiro, Rita; Santos, Susana; Almeida, José; Pires, Maria João; da Costa, Rui Miguel Gil; Córdova, Cláudia; Nogueira, António; Neuparth, Maria João; Medeiros, Rui; Bastos, Margarida Maria da Silva Monteiro; Gaivão, Isabel; Peixoto, Francisco; Oliveira, Maria Manuel; Oliveira, Paula Alexandra (2019). The cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observations. International Journal of Molecular Sciences. ISSN 1661-6596. 20, p.en_EN
dc.identifier.doi10.3390/ijms20163902en_EN
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10198/20272
dc.language.isoeng
dc.peerreviewedyesen_EN
dc.subjectCOX-2en_EN
dc.subjectIn vivoen_EN
dc.subjectK14HPV16en_EN
dc.subjectNSAIDen_EN
dc.titleThe cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observationsen_EN
dc.typejournal article
dspace.entity.typePublication
person.familyNameNogueira
person.givenNameAntónio José M.
person.identifier.ciencia-id8A11-794E-36BD
person.identifier.orcid0000-0001-8912-7355
person.identifier.scopus-author-id55865568268
rcaap.rightsopenAccessen_EN
rcaap.typearticleen_EN
relation.isAuthorOfPublication648209a2-eec9-4bec-975a-32673e41b95c
relation.isAuthorOfPublication.latestForDiscovery648209a2-eec9-4bec-975a-32673e41b95c

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