Browsing by Author "Pinto, Rui"
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- Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia-reperfusion in the ratPublication . Bignotto, Leticia; Rocha, Joao; Sepodes, Bruno; Eduardo-Figueira, Maria; Pinto, Rui; Chaud, Marco; de Carvalho, Joao; Moreno, Heitor,; Mota-Filipe, HelderThe regular intake of tomatoes or its products has been associated with a reduced risk of chronic diseases and these effects have been mainly attributed to lycopene. Here, we evaluated the anti-inflammatory properties of lycopene and its protective effects on organ injury in two experimental models of inflammation. In order to study the effects of lycopene in local inflammation, a carrageenan-induced paw oedema model in rats was performed. Lycopene was administered as an acute (1, 10, 25 or 50 mg/kg, intraperitoneally, 15 min before carrageenan injection) and chronic treatment (25 or 50 mg/kg per d, 14 d). Inflammation was assessed by the measurement of paw volume increase after 6 h. Lycopene significantly inhibited paw oedema formation at two doses (25 and 50 mg/kg) in both acute and repeated administration. The effect of lycopene on liver inflammation was evaluated in a liver ischaemia-reperfusion (I/R) model. Rats were subjected to 45 min of ischaemia of three-quarters of the liver followed by 2h of reperfusion. In this model, lycopene was administered daily at two doses (25 and 50mg/kg) during the 14d that preceded the experiments. Repeated administration of lycopene reduced liver injury induced by I/R, as demonstrated by the reduction of the increase in liver injury markers (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyl transferase) and attenuation of liver tissue lipoperoxidation was evidenced by a decrease in malondialdehyde production. The present results show that lycopene exhibited local anti-inflammatory activity and also attenuated liver injury induced by I/R. We speculate that lycopene administration might be useful in the pharmacological modulation of inflammatory events.
- Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesisPublication . Parada, Belmiro; Sereno, Jose; Reis, Flavio; Teixeira-Lemos, Edite; Garrido, Patricia; Pinto, Angela Filipa; Cunha, Maria Fernanda; Pinto, Rui; Mota, Alfredo; Figueiredo, Arnaldo; Teixeira, FredericoPurpose: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention. Results: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGF beta 1 and CRP and increase TNF alpha and IL-1 beta (p 0.001); (V) CEL reduced MDA formation in serum (p 0.001) and liver (p 0.05) and also showed a trend to reduction in kidney. Methods: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. Conclusions: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition.
- Combined efects of dietary Laminaria digitata with alginate lyase on plasma metabolites and hepatic lipid, pigment and mineral composition of broilersPublication . Costa, Mónica; Lopes, Paula Alexandra; Assunção, JMP; Alfaia, Cristina; Coelho, Diogo; Mourato, Miguel; Pinto, Rui; Lordelo, Maria; Prates, JAMABSTRACT - Background: The Laminaria digitata is an abundant macroalga and a sustainable feedstock for poultry nutrition. L. digitata is a good source of essential amino acids, carbohydrates and vitamins, including A, D, E, and K, as well as triacylglycerols and minerals, in particular iron and calcium. However, the few studies available in the literature with broilers document the application of this macroalga as a dietary supplement rather than a feed ingredient. No study has addressed up until now the efects of a high-level incorporation (>2% in the diet) of L. digitata on plasma biochemical markers and hepatic lipid composition, as well as minerals and pigments profle in the liver of broilers. Our experimental design included one hundred and twenty Ross 308 male birds contained in 40 wired-foor cages and distributed to the following diets at 22days of age (n=10) for 15days: 1) a corn-soybean basal diet (Control); 2) the basal diet plus 15% of L. digitata (LA); 3) the basal diet plus 15% of L. digitata with 0.005% of Rovabio® Excel AP (LAR); and 4) the basal diet plus 15% of L. digitata with 0.01% of the recombinant CAZyme, alginate lyase (LAE).
- Contribution to the Preclinical Safety Assessment of Lannea velutina and Sorindeia juglandifolia LeavesPublication . Malú, Quintino; Lima, Katelene; Malmir, Maryam; Pinto, Rui; da Silva, Isabel Moreira; Catarino, Luís; Duarte, Maria Paula; Serrano, Rita; Rocha, João; Lima, Beatriz Silva; Silva, Olgafirst_pagesettingsOrder Article Reprints Open AccessArticle Contribution to the Preclinical Safety Assessment of Lannea velutina and Sorindeia juglandifolia Leaves by Quintino Malú 1,Katelene Lima 1,Maryam Malmir 1,Rui Pinto 1,2,Isabel Moreira da Silva 1ORCID,Luís Catarino 3ORCID,Maria Paula Duarte 4,Rita Serrano 1ORCID,João Rocha 1ORCID,Beatriz Silva Lima 1 andOlga Silva 1,*ORCID 1 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal 2 Dr Joaquim Chaves Laboratório de Análises Clínicas, 2790-224 Carnaxide, Portugal 3 Centre for Ecology, Evolution and Environmental Changes, (cE3c) & CHANGE-Global Change and Sustainability Institute, Faculty of Sciences, Universidade de Lisboa, 1749-016 Lisboa, Portugal 4 MEtRICs/Chemical Department, Nova School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal * Author to whom correspondence should be addressed. Plants 2023, 12(1), 130; https://doi.org/10.3390/plants12010130 Received: 5 December 2022 / Revised: 20 December 2022 / Accepted: 21 December 2022 / Published: 27 December 2022 (This article belongs to the Special Issue Medicinal Plant Extracts) Download Browse Figures Versions Notes Abstract Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. (family Anacardiaceae) are used in African traditional medicine. Although these medicinal plants have widespread use in the treatment of inflammatory diseases, there is no scientific data concerning their preclinical or clinical safety. This work aimed to investigate the phytochemical properties of the leaves of both species using HPLC-UV/DAD, as well as the in vivo oral repeated-dose toxicity of 70% hydroethanolic leaf extract of S. juglandifolia and the in vitro genotoxicity of 70% hydroethanolic leaf extracts of L. velutina and S. juglandifolia. Clinical signs of toxicity, body weight variations, and changes in food consumption, mortality, and blood biochemical parameters were monitored. Genotoxicity was assessed using the bacterial reverse mutation assay (Ames test) with and without metabolic activation, according to OECD guidelines. The obtained results showed the presence of gallic acid and anacardic acid as the main marker constituents in both species. No significant changes in general body weight or food intake were observed; small significant changes with no critical relevance were observed in the blood biochemistry of animals treated with S. juglandifolia hydroethanolic extract (50, 400, and 1000 mg/kg body weight) compared to those in the control group. No genotoxicity was observed in the bacterial reverse mutation assay with S. juglandifolia and L. velutina extracts (up to 5 mg/plate). The safety data obtained in vivo and lack of genotoxic potential in vitro points to the safe medicinal use of S. juglandifolia and L. velutina extracts.
- Diet supplementation with the cis-9,trans-11 conjugated linoleic acid isomer affects the size of adipocytes in Wistar ratsPublication . Lopes, Paula A.; Martins, Susana V.; Pinho, Mario S.; Alfaia, Cristina M.; Fontes, Carlos M. G. A.; Rodrigues, Pedro O.; Morais, Graqa S. L.; Castro, Matilde F.; Pinto, Rui; Prates, Jose A. M.Previous reports have demonstrated that conjugated linoleic acid (CLA) acts on body fat accumulation in a variety of animal models. The aim of the present study was to investigate the effect of cis (c)-9,trans (t)-11 and t10,c12 CLA isomers on the number and size of adipocytes from the inguinal and retroperitoneal fats in Wistar male rats. A 5.1% palm oil-based diet was supplemented with CLA isomers as follows: 0.6% of c9,t11, 0.6% of t10,c12, 1.3% of c9,t11 and t10,c12 isomers in mixture, and a control nonsupplemented group for comparative purposes. Fat tissues were prepared on microscope slides for histologic examination using an image-analysis software to count the number of adipocytes and measure cell sizes. The results showed that CLA isomers did not affect (P .05) either final body and fat depot weights or serum lipids (with the exception of triacylglycerols) and adipocytokines (leptin and adiponectin). Animals fed the c9, t11 CLA isomer diet showed larger adipocytes when compared to other groups. Independently of the CLA dietary treatment, retroperitoneal fat showed larger adipocytes (3319 mu m(2)) and therefore a smaller number of adipocytes per unit of area, compared to inguinal fat (3055 mu m(2)) Taken together, the data suggest that a palm oil-based diet supplemented with the c9,t11 CLA isomer in Wistar rats, in contrast to the t10,c12 isomer and the mixture of both isomers, increases adipocyte dimensions in inguinal and retroperitoneal fat depots, while having a minor effect in serum lipids and adipocytokines. (c) 2008 Elsevier Inc. All rights reserved.
- Erythropoietin Promotes Deleterious Cardiovascular Effects and Mortality Risk in a Rat Model of Chronic Sports DopingPublication . Piloto, Nuno; Teixeira, Helena M.; Teixeira-Lemos, Edite; Parada, Belmiro; Garrido, Patricia; Sereno, Jose; Pinto, Rui; Carvalho, Lina; Costa, Elisio; Belo, Luis; Santos-Silva, Alice; Teixeira, Frederico; Reis, FlavioAthletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate the cardiovascular effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was performed in four male Wistar rat groups: control-sedentary; rhEPO-50 IU kg(-1), 3 times/wk; exercised (EX)-swimming for 1 h, 3 times/wk; EX + rhEPO. One rat of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat's tissues presented brain with vascular congestion; left ventricular hypertrophy, together with a "cardiac-liver", suggesting the hypothesis of heart failure as cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians.
- Evaluation of the diagnostic performance of the rapid test VIKIA HIV1/2 in a highly complex HIV-1 epidemicPublication . Santos, Ângela; Clemente, Sofia; Bártolo, Inês; Palladino, Claudia; Cavaco-Silva, Patrícia; Franco, Verónica; Epalanga, Marta; Pinto, Rui; Taveira, NunoThe rapid test VIKIA HIV1/2 was evaluated in 210 Angolan subjects infected with multiple HIV-1 subtypes and complex recombinant forms and 225 seronegative individuals. All infected subjects tested positive (100% sensitivity); all seronegative subjects tested negative (100% specificity). VIKIA HIV1/2 is highly specific and sensitive even in highly complex epidemics.
- Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in womenPublication . Bártolo, Inês; Diniz, Ana Rita; Borrego, Pedro; Ferreira, João Pedro; Bronze, Maria Rosário; Barroso, Helena; Pinto, Rui; Cardoso, Carlos; Pinto, João F.; Diaz, Rafael Ceña; Broncano, Pilar Garcia; Muñoz-Fernández, Maria Angel; Taveira, NunoMicrobicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.
- Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in womenPublication . Bártolo, Inês; Diniz, Ana Rita; Borrego, Pedro; Ferreira, João Pedro; Bronze, MR; Barroso, Helena; Pinto, Rui; Cardoso, Carlos; Pinto, João F.; Ceña Diaz, Rafael; Broncano, Pilar Garcia; Muñoz-Fernandez, Maria Angel; Taveira, NunoMicrobicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.
- Exercise training is associated with improved levels of C-reactive protein and adiponectin in ZDF (type 2) diabetic ratsPublication . de Lemos, Edite Teixeira; Reis, Flavio; Baptista, Sofia; Pinto, Rui; Sepodes, Bruno; Vala, Helena; Rocha-Pereira, Petronila; Silva, Alice Santos; Teixeira, FredericoBackground: Chronic tow-grade systemic inflammation is a feature of such chronic diseases as cardiovascular disease and type 2 diabetes (T2D). There is evidence that regular exercise is effective as a treatment in these situations. This study intended to assess the levels of two inflammatory mediators, C-creative protein (CRP) and adiponectin, in Zucker Diabetic Fatty (ZDF, fa/fa) rats, an experimental model of T2D, and to determine whether exercise-induced changes in insulin resistance could be explained by modifications in these inflammation markers. Material/Methods: Male ZDF (Gmi fa/fa) rats and their littermates (Gmi +/+), aged 8 weeks, were randomly assigned in two groups: an exercise trained and a sedentary one. Swimming was conducted 1 h/day 3 days/week for 12 weeks. The rats were sacrificed 48 h after the last rotund of exercise. Rats had their body weight, insulin, adiponectin, CRP, as well as glucose, total cholesterol, triglycerides, MDA, and SOD measured and HOMA-IR calculated before and after the 12-week swimming training. Results: In the ZDF (fa/fa) rats underwent swimming exercise, all the metabolic abnormalities were totally or partially prevented (p 0.001), namely the hyperglycemic, hyperinsulinemic, and dyslipidemic pattern observed in their sedentary counterparts. Furthermore, even without body weight change, a plasma adiponectin increase (28.0%) and a CRP decrease (12.7%) were also observed. Conclusion: A 12-week thrice-weekly swimming training was associated with improved measures of chronic inflammation markers as measured by adiponectin and CRP. Moreover, improvements in insulin sensitivity resulting from swimming exercise appeared to be related to changes in these inflammatory mediators.
