Browsing by Author "Oliveira, Maria Manuel"
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- The cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observationsPublication . Ferreira, Tiago; Campos, Sandra; Silva, Mónica; Ribeiro, Rita; Santos, Susana; Almeida, José L.S.; Pires, Maria João; Costa, Rui Miguel Gil; Córdova, Cláudia; Nogueira, António José M.; Neuparth, Maria João; Medeiros, Rui; Bastos, Margarida M.S.M.; Gaivão, Isabel; Peixoto, Francisco P.; Oliveira, Maria Manuel; Oliveira, Paula A.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.
- The effects of long-term chaetomellic acid a administration on renal function and oxidative stress in a rat model of renal mass reductionPublication . Nogueira, António José M.; Peixoto, Francisco P.; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno Jorge; Oliveira, Paula A.; Pires, Maria JoãoThis study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in amodel of renalmass reduction. Methods.MaleWistar ratswere subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAAadministration significantly increased catalase andGR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio.No significant differences were found between theRMRgroups in any of the parameters of renal function.However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.
- Oxidative stress responses and histological hepatic alterations in barbel, Barbus bocagei, from Vizela river, PortugalPublication . Peixoto, Francisco P.; Carrola, João; Coimbra, Ana Maria; Fernandes, Conceição; Teixeira, Paulo; Coelho, Luís; Conceição, Ivo; Oliveira, Maria Manuel; Fontaínhas-Fernandes, A.Barbel (Barbus bocagei) a common species in Portuguese rivers was studied to assess the impact of water contamination on hepatic oxidative stress response, lipid peroxidation and histology. The Vizela River is a tributary of the Ave River, located in one of the most industrialized areas of Portugal. The oxidative stress biomarkers analyzed included superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, glucose 6‑phosphate dehydrogenase and xanthine oxidase activities. Levels of reduced glutathione and lipid peroxidation were also evaluated. Except xanthine oxidase activity, that did not show any alteration, all the other enzymatic activities were increased in the liver of barbel captured in the Vizela River when compared with reference barbel. While, no differences were observed for glutathione reductase content, lipid peroxidation was higher in barbel from the Vizela River. Liver histological alterations were determined and their severity scored. Though lymphocyte foci were only observed in Vizela River barbel, macrophage aggregates were also present in reference barbel, although the severity score was higher in Vizela fish. The results of this study show that barbel liver oxidative stress responses, lipid peroxidation and histology are sensitive to the contaminants present in Vizela River water and are valuable biomarkers for monitoring purposes.