Browsing by Author "Ferreira, Tiago"
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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.
- Cytinus hypocistis (L.) L. extract effects in an animal model of papillomavirus-induced neoplasiaPublication . Medeiros, Catarina; Silva, Ana Rita; Ferreira, Tiago; Barros, Lillian; Neuparth, Maria João; Peixoto, Francisco P.; Bastos, Margarida M.S.M.; Medeiros, Rui; Costa, Rui Miguel Gil; Pires, Maria João; Faustino-Rocha, Ana; Gama, Adelina; Oliveira, Paula A.Infections with certain types of papillomavirus, such as the human papillomavirus 16 (HPV16), are associated with the development of preneoplastic lesions and cancers of the anogenital, and head and neck regions. Cytinus hypocistis (L.) L. extracts are composed of substances presenting antiproliferative, antioxidant, anti-inflammatory and antibacterial properties, which might be promising as new therapeutic compounds. This study analysed the influence of topical application of an extract obtained from C. hypocistis (CH) on K14-HPV16 and FVB/n mice to evaluate its therapeutic and toxicological properties. To achieve the study goals, 30 female mice, 33–37 weeks old, were divided into six groups (n=5/group): I (HPV+CH3.1); II (HPV+CH6.2); III (HPV+CH12.4); IV (FVB/ n+CH12.4); V (HPV+control) and VI (FVB/n+control). CH was applied topically to both ears for 28 days. After this period, all animals were sacrificed for samples collection. Skin lesions were classified histologically. Toxicological parameters included haematological and biochemical blood markers, and hepatic oxidative stress analysis. Transgenic animals showed a decrease in mean body weight regardless of the concentration of extract applied. The extract had no influence on physiological parameters, organ weight, or biochemical and oxidative stress parameters. Histology demonstrated the presence of proliferative epithelial lesions in the skin and oral mucosa of K14-HPV16 mice, with no association with the application of this extract. Overall, the application of CH extract had no influence on the skin lesions and was well tolerated by the animals in these concentrations.
- Dietary supplementation with chestnut (Castanea sativa) reduces abdominal adiposity in FVB/n mice: a preliminary studyPublication . Rodrigues, Pedro M.; Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Seixas, Fernanda; Costa, Rui Miguel Gil; Martins, Tânia; Neuparth, Maria João; Pires, Maria João; Lanzarin, Germano; Félix, Luís; Venâncio, Carlos; Ferreira, Isabel C.F.R.; Bastos, Margarida M.S.M.; Medeiros, Rui; Gaivão, Isabel; Rosa, Eduardo; Oliveira, Paula A.The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the e ects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet; 2 fed a diet supplemented with 0.55% (w/w) chestnut; and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant di erences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.
- Exploring the Chemopreventive and Antioxidant Effects of Spearmint Leaf Hydroethanolic Extract in HPV16-transgenic MicePublication . Jesus, Tiago M.; Azevedo, Tiago; Silva-Reis, Rita; Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Medeiros, Catarina; Ferreira, João; Gama, Adelina; Gaivão, Isabel; Pires, Maria João; Lanzarin, Germano; Félix, Luís; Venância, Carlos; Medeiros, Rui; Bastos, Margarida M.S.M.; Finimundy, Tiane C.; Barros, Lillian; Costa, Rui M. Gil da; Oliveira, Paula A.Human papillomavirus (HPV) is the most common sexually transmitted infectious agent and, in cases of persistent infection, may cause cancer. This study evaluated the toxicological and antitumor properties of Mentha spicata extract (MSE) in KP14HPV16 mice, which carry HPV16 oncogenes. Thirty‑three female FVB/n mice (Mus musculus), including 17 HPV‑transgenic and 16 wild‑type (WT) mice, were divided into six groups. The control groups received tap water (WT‑C, n=5, and HPV‑C, n=6), while the treatment groups received either 0.50 mg/ml MSE (WT‑50 and HPV‑50, n=6) or 0.55 mg/ml MSE (WT‑55 and HPV‑55, n=5) in drinking water for 28 days. Afterwards, animals were sacrificed, and blood and organs were collected for histopathological and biochemical analysis. The main phenolic compounds in MSE were rosmarinic acid and luteolin‑O‑glucoronide. MSE did not significantly affect weight gain in WT mice; however, WT‑55 gained significantly more weight than HPV‑55. MSE demonstrated antioxidant activity as indicated by the modulation of hepatic superoxide dismutase and glutathione S‑transferase (GST) activity, as well as renal GST activity, in MSE‑treated HPV groups. MSE did not reduce histological lesion incidence or systemic inflammation in HPV16‑transgenic mice. In general, while MSE was safe and exhibited antioxidant activity, it did not significantly impact HPV16‑induced lesions, warranting further research to assess systemic effects with different concentrations and durations.
- Ganoderma Lucidum effects in an animal model of obesityPublication . Castro-Ribeiro, Catarina; Silva-Reis, Rita; Mendes-Gonçalves, Mariana; Ferreira, Tiago; Taofiq, Oludemi; Barros, Lillian; Martins, Tânia; Faustino-Rocha, Ana; Pires, Maria João; Pinto, M.L.; Ferreira, Isabel C.F.R.; Venâncio, Carlos; Rosa, Eduardo; Oliveira, Paula A.Obesity is a pandemic disease, and its evolution can be influenced by regular consumption of natural bioactive compounds. Mushrooms, such as Ganoderma lucidum (GL), include a wide variety of biomolecules with potential anti-obesity effects. This work aimed to study the influence of GL in an animal model of obesity. Forty-eight male mice (C57BL/6J) were divided into 5 groups: Group (G)-1-Western Control Diet; G-2-Western Diet 0.2% Cholesterol (WDC); G-3-WDC+0.7g/kg of GL; G-4-WDC+1.4g/ kg of GL; G-5 WDC+2.8g/kg of GL. Water and food consumption were recorded weekly. Animals were weighed individually, and their temperature was measured on the back and abdomen (thermographic camera FLIRE6390). Thirteen weeks later, animals were sacrificed, and organs collected. A liver portion was used for histopathology analysis (ethical approval nº 8776). Chemical characterization of the GL extract was profiled by HPLC-DAD-ESI/MS. Ganoderic acid H and p-hydroxybenzoic acid were the main triterpenic and phenolic acids in the extract, respectively. Food and water consumption were no different among groups. All animals showed weight gain (11-16%): animals without GL supplementation showed the highest weight gain (G2 and G1, respectively); the groups with GL showed the lowest weight gain, which decreased as the mushroom concentration increased. Basal and final body temperatures remained constant. Liver weight was different among groups (p<0.05). Microvesicular (39/47; 83%) and macrovesicular fatty changes (steatosis) were the most frequent morphological changes in the liver. Hyperlipidemic diets consumption promoted weight gain and obesity. The higher weight gain in the groups not supplemented with GL suggested its anti-obesity properties. In this study, animals developed steatosis, which was not modified by GL supplementation. However, it should be noticed that the changes in lipid metabolism are reversible, and the differences observed in the liver relative weights, lower in the groups supplemented with GL, suggested an ongoing process of restoring to normal hepatocyte’s phenotype.
- Histological lesions in hpv16-transgenic model: the effect of hidroethanolic extract of Lavandula pedunculata (mill.) Cav.Publication . Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Moutinho, Magda S.S.; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Rosa, Eduardo; Oliveira, Paula A.The K14HPV16 mice is a skin squamous carcinoma model that can be used to test antitumoral properties of several chemical and natural compounds1. Lavandula penduculata (Mill.) Cav., known as lavender, belongs to the Laminaceae family and has been used in traditional medicine as infusions to treat several conditions2. This work aimed to evaluate the effects of the hydroethanolic French lavender extract (FLE) in an HPV16-transgenic mice model lesions. The extract was obtained through a maceration with ethanol/water (80:20, v/v) and its phenolic composition was determined by HPLC-DADESI/ MS. The FLE was dissolved in drinking water at 6.8 mg/10mL/animal and the animals were supplemented during 29 consecutive days. Twentyeight male mice were randomly divided into four groups: (n=7/group): group I (HPV16- control); II (HPV16- FLE); III (HPV16+ control) and IV (HPV16+ FLE). After 29 days all animals were sacrificed by xylazineketamine overdose following cardiac puncture to obtain blood samples. Skin samples (chest and ear), kidney, liver and spleen were processed for histological analysis.A total of thirteen compounds were identified in the hydroethanolic extract, being salvianolic acid B and rosmarinic acid the main molecules present. Moreover, the compounds revealed to be stable in the drinking water for 5 days. Histological analyses of skin samples from wild-type mice exposed (group II) and not exposed (group I) to FLE showed normal skin histology. Group III showed skin chest epidermal hyperplasia in 100% of the mice while group IV showed less epidermal hyperplasia frequency (66.6%) (p>0.05). Concerning to liver, kidney, and spleen lesions there are no differences between groups (p>0.05). The lavender extract did not prevent the progression of HPV-16 induced cutaneous lesions in this model. These data deserve more investigation to clarify the effect of lavender extract on HPV-16 lesions.
- Histological lesions in hpv16-transgenic model: the effect of hidroethanolic extract of Lavandula pedunculata (mill.) Cav.Publication . Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Moutinho, Magda S.S.; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Rosa, Eduardo; Oliveira, Paula A.The K14HPV16 mice is a skin squamous carcinoma model that can be used to test antitumoral properties of several chemical and natural compounds1. Lavandula penduculata (Mill.) Cav., known as lavender, belongs to the Laminaceae family and has been used in traditional medicine as infusions to treat several conditions2. This work aimed to evaluate the effects of the hydroethanolic French lavender extract (FLE) in an HPV16-transgenic mice model lesions. The extract was obtained through a maceration with ethanol/water (80:20, v/v) and its phenolic composition was determined by HPLC-DADESI/ MS. The FLE was dissolved in drinking water at 6.8 mg/10mL/animal and the animals were supplemented during 29 consecutive days. Twentyeight male mice were randomly divided into four groups: (n=7/group): group I (HPV16- control); II (HPV16- FLE); III (HPV16+ control) and IV (HPV16+ FLE). After 29 days all animals were sacrificed by xylazineketamine overdose following cardiac puncture to obtain blood samples. Skin samples (chest and ear), kidney, liver and spleen were processed for histological analysis.A total of thirteen compounds were identified in the hydroethanolic extract, being salvianolic acid B and rosmarinic acid the main molecules present. Moreover, the compounds revealed to be stable in the drinking water for 5 days. Histological analyses of skin samples from wild-type mice exposed (group II) and not exposed (group I) to FLE showed normal skin histology. Group III showed skin chest epidermal hyperplasia in 100% of the mice while group IV showed less epidermal hyperplasia frequency (66.6%) (p>0.05). Concerning to liver, kidney, and spleen lesions there are no differences between groups (p>0.05). The lavender extract did not prevent the progression of HPV-16 induced cutaneous lesions in this model. These data deserve more investigation to clarify the effect of lavender extract on HPV-16 lesions.
- Supplementation of an anthocyanin-rich elderberry (Sambucus nigra L.) extract in FVB/n mice: a healthier alternative to synthetic colorantsPublication . Azevedo, Tiago; Ferreira, Tiago; Ferreira, João Miguel Mendes; Teixeira, Filipa; Ferreira, Diana; Silva-Reis, Rita; Neuparth, Maria João; Pires, Maria João; Pinto, Maria de Lurdes; Costa, Rui Miguel Gil; Bastos, Margarida M.S.M.; Medeiros, Rui; Felix, Luis; Venâncio, Carlos; Dias, Maria Inês; Gaivão, Isabel; Barros, Lillian; Oliveira, Paula A.Featured Application Due to anthocyanins' potential as colorants, this anthocyanin-rich elderberry extract presents a healthier alternative to commercially available colorants and has the potential to be used at industry level. Sambucus nigra L., popularly known as elderberry, is renowned for its amazing therapeutic properties, as well as its uses as a food source, in nutraceuticals, and in traditional medicine. This study's aim was to investigate the effects of an elderberry extract (EE) on mice for 29 days, as well as the safety of the extract when used as a natural colorant. Twenty-four FVB/n female mice (n = 6) were randomly assigned to one of four groups: control, 12 mg/mL EE (EE12), 24 mg/mL EE (EE24), or 48 mg/mL EE (EE48). The predominant anthocyanins detected were cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. Food and drink intake were similar between groups, with the exception of EE48, who drank significantly less compared with the Control. Biochemical analysis of the liver showed that the changes observed in histological analysis had no pathological significance. The EE, at doses of 24 and 48 mg/mL, significantly reduced the oxidative DNA damage compared with the non-supplemented group. The S. nigra extract showed a favorable toxicological profile, affording it potential to be used in the food industry.
- Therapeutic properties of Tilia platyphyllos Scop. in K14HPV16 micePublication . Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Gama, Adelina; Costa, Rui Miguel Gil; Neuparth, Maria João; Lanzarin, Germano; Venâncio, Carlos; Félix, Luís; Pires, Maria João; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Rosa, Eduardo; Oliveira, Paula A.Tila platyphyllos Scop. is a popular broad-leave tree, native to central and southern Europe