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

article

Ferreira, Tiago
Campos, Sandra
Silva, Mónica G
Ribeiro, Rita
Santos, Susana
Almeida, José
Pires, Maria João
Gil da Costa, Rui Miguel
Marcos, Cláudia Córdova
Nogueira, António
Neuparth, Maria João
Medeiros, Rui
Bastos, Margarida Maria da Silva Monteiro
Gaivão, Isabel
Peixoto, Francisco
Oliveira, Maria Manuel
Oliveira, Paula Alexandra

Ferreira, 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/ijms20163902

1422-0067

10.3390/ijms20163902

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

Animals
Anticarcinogenic agents
Cyclooxygenase 2 Inhibitors
Female
Human papillomavirus 16
Isoxazoles
Mice
Mice transgenic
Papillomavirus infections
Skin
Skin neoplasms

info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FAGR%2F04033%2F2019/PT
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FCVT%2F00772%2F2019/PT
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FEQU%2F00511%2F2019/PT

2020-11-24T10:47:14Z
2020-11-24T10:47:14Z
2019

Carcinogenesis 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.
info:eu-repo/semantics/publishedVersion

openAccess
http://creativecommons.org/licenses/by/4.0/

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