Advisor(s)
Abstract(s)
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 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.
Description
Keywords
COX-2 In vivo K14HPV16 NSAID
Pedagogical Context
Citation
Ferreira, 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.