Navegando por CNPq "CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA BIOQUIMICA E MOLECULAR"

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Acesso aberto (Open Access)
Apocinina reverte fibrose e disfunção elétrica cardíaca induzida pelo aumento sistêmico de MMP-2 em camundongos adultos
(Universidade Federal do Pará, 2024-09) PONTES, Maria Helena Barbosa Pontes; RODRIGUES, Keuri Eleutério; http://lattes.cnpq.br/0030683756521893; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; https://orcid.org/0000-0001-7495-9837
Heart failure (HF) is characterized by the heart's inability to maintain adequate tissue blood flow, associated with deficits in contraction and relaxation, due to either an acute or chronic injurious event. Matrix metalloproteinase 2 (MMP-2) is linked to the pathogenesis and pathophysiology of HF, promoting proteolysis of contractile proteins and oxidative stress. Rescue therapies that directly or indirectly modulate MMP-2 activity could help improve cardiac remodeling and dysfunction. Apocynin inhibits NADPH oxidase, thereby attenuating oxidative stress. This study hypothesizes that apocynin can reverse cardiac remodeling and electrical dysfunction induced by MMP-2 by preventing oxidative imbalance. The aim of this study is to evaluate the effect of apocynin on oxidative imbalance and cardiac remodeling induced by systemic MMP-2 increase in adult mice. Adult male C57BL/6 mice were subjected to two experimental protocols. First, the animals underwent a time course protocol and were divided into two groups: the vehicle group received 0.9% saline via intraperitoneal (ip) injection, and the MMP-2 group received MMP-2 (150 ng/g body weight) via ip injection, for up to 4 weeks. Subsequently, a treatment protocol with apocynin was performed, starting 4 weeks after the cessation of MMP-2 administration. During this period, the animals were divided into four experimental groups: 1) vehicle (received water via gavage); 2) apocynin (50 mg/kg via gavage); 3) MMP-2 (received water via gavage); and 4) MMP-2 + apocynin (50 mg/kg via gavage). At the end of the protocols, all animals underwent electrocardiography, and then their hearts were collected for morphological and biochemical evaluation. During the time course, the MMP-2 group showed increased gelatinolytic activity, oxidative imbalance, fibrosis, decreased heart rate, along with increased RR, PQ, QT, and QTc intervals from the first week of administration, effects that persisted over the four weeks, even without MMP-2 administration. Treatment with apocynin reversed the increase in MMP-2 activity and expression in the heart, as well as oxidative imbalance, lipid peroxidation, hypertrophy, cardiac fibrosis, and electrical dysfunction. We conclude that systemic MMP-2 increase can promote cardiac remodeling through increased MMP-2 activity and expression in cardiac tissue, leading to redox imbalance and electrical dysfunction, and that apocynin treatment was able to reverse the effects induced by MMP-2, suggesting that these effects are dependent on oxidative imbalance and NADPH oxidase.
Acesso aberto (Open Access)
Atividade antiplasmodial e modelagem molecular de novas chalconas e derivados
(Universidade Federal do Pará, 2008) PEREIRA, Glaécia Aparecida do Nascimento; RIBEIRO, Cláudio Tadeu Daniel; http://lattes.cnpq.br/0814854098256062; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Malaria is an infection caused by Plasmodium sp. and It can be serious, if not treated precociously. It affects significant fraction of humanity and has profound health impact worldwide. It is estimated that 3.3 billion people are exposed to the risk of transmission. One of the problems of the infection is the growing emergence of parasite resistance to antimalarial drugs. In this context, studies are needed to develop new alternative chemotherapy. Many substances, such as the chalcones, have had their antiplasmodial activity proven. However, the physicochemical properties of these molecules, which are important for biological actions, are not well established. In this work, molecular modeling was performed and the antiplasmodial activity was evaluated of two chalcones (HBR1, and LH2) and four derivatives of chalcones (GH3, IV4, LCH1, and LCH3). For that, we determined the drug concentration inhibitory of 50% of the growth of P. falciparum in vitro as well as the physicochemical properties of derivatives of chalcones as HOMO, LUMO, electrostatic potential, C log P, hydration energy, polarizability and molecular volume through virtual calculations. The results of the calculated values were correlated with the biological activity in order to identify chemical parameters that can influence the antiplasmodial action. The inhibitory concentrations in 50% of the growth of P. falciparum ranged from 0,2 to 1,7 M, and these values were smaller than described them in the literature. The study of the correlation between the biological activities and the physicochemical properties showed determinating parameters for the biological activity, as LUMO, electrostatic potential, C log P and hydration energy, which may help in the selection of molecules more active against P. falciparum. Thus, these molecular properties can be used in the rational planning of new chalcones and/or derivatives with antiplasmodial activity.
Acesso aberto (Open Access)
Caracterização do mecanismo de ação antiinflamatória do flavonóide BAS1 isolado da planta Brosimum acutifolium
(Universidade Federal do Pará, 2011-08-02) MORAES, Waldiney Pires; SILVA, Anderson Manoel Herculano Oliveira da; DINIZ, Domingos Luiz Wanderley Picanço; http://lattes.cnpq.br/9601463988942971
Inflammation is the body's response to injury and danger. Even though it’s a body defensive mechanism, this response’s intensity and/ or persistency might be harmful for an individual. In such context, natural products are important sources of biologically active molecules, and they’re considered promising resources for the discovering of new drugs. Based on ethno pharmacological studies, BAS1 flavonoid (4'-hydroxy, 7, 8 - (2'', 2''-dimethyl-pyran)-flavan), which hasn’t been described by literature yet, was isolated from the Brosimum acutifolium plant, popularly known as "mururé da terra-firme." Facing this, the present study aimed at characterizing the anti-inflammatory mechanism of action of BAS1 flavonoid in stimulated murine macrophages. Macrophages were activated with LPS and IFN-γ, cell viability was evaluated by the MTT, levels of inflammatory mediators were determined by ELISA (TNF-α, PGE2, IL-10) through Griess reaction (NO) and protein expression by Western blotting. The results demonstrate that BAS1 only has cyclotoxic effects at high concentrations (100 μM) inhibited NO production (95%), negatively regulated the expression of NOS-2, reduced the TNF-α production (39%) and PGE2 (57%), but didn’t with IL-10 in activated macrophages. Thus, demonstrating the pharmacological effect of BAS1 flavonoid, as well as supporting the usage of the Brosimum acutifolium plant as an anti-inflammatory in our region was an important contribution from this study. Furthermore, the production of this plant’s extract could provide the local population with an effective and affordable anti-inflammatory. The present work may also contribute to the establishment of a new classification of anti-inflammatory agents, based on natural flavonoids, such as BAS1.
Acesso aberto (Open Access)
Diagnóstico citológico e molecular da infecção pelo HPV em mulheres do município de Barcarena, Pará, Norte do Brasil
(Universidade Federal do Pará, 2010-06-02) NASCIMENTO, Ludmila Marcia Sousa do; BRITO JUNIOR, Lacy Cardoso de; http://lattes.cnpq.br/9705670940390281; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
HPV (human papillomavirus) was appointed by the WHO (World Health Organization - WHO) as the main risk factor for developing cervical cancer, thus becoming an important and very serious public health problem, especially in underdeveloped countries or under development. The early sexual activity, multiple partners and casual sex, smoking, immunosuppression (eg, the population of AIDS patients), pregnancy, sexually transmitted diseases like herpes and chlamydia prior, in addition to non-compliance with the measures already taken to prevent Sexually Transmitted Diseases (STDs), such as the simple use of condoms is admittedly associated with the incidence of HPV infection. This research aimed to evaluate the diagnostic performance of the methodologies of conventional cytology (Pap test) compared to liquid based cytology, and to determine the prevalence of genotypes 16 and 18 of HPV in women without HPV cytopathic effect compatible with and relate to presence of inflammatory conditions, or not associated with HPV, with epidemiological data such as age, education, socio-cultural condition of women from the municipality of Barcarena - Pará - Brazil. To do so, in this study voluntarily, 50 women attended at the Health Unit Barcarena - Brazil, through the campaign to collect Pap test as a method of preventing cancer of the cervix. These women were informed about all procedures performed by the body of this health study and the results of this search and only after the volunteers have signed the Deed of Consent, they were included for sampling. The analysis and test results of liquid based cytology and conventional were performed according to the Bethesda Classification and reviewed blindly by two pathologists. For the analysis statistic was used Fisher's exact test and the "Screening Test" to determine the specificity / sensitivity of the methods, considering the significant value of p ≤ 0.05. Our results indicate that the use of liquid based cytology has demonstrated a number of advantages over conventional cytology. In molecular diagnostics (PCR) were observed occurrences of HPV types 16 and 18 in 10% of women attended. Among the cases that were PCR positive for types 16 and 16/18 most of the women were 27.4 years old on average, with more schooling, performing household chores and rural areas, and with instances of co-infection by infectious agents cause other sexually transmitted diseases. The results of this study reinforce the importance of maintaining free campaigns to prevent cervical cancer as a preventive measure in combating this disease, especially in Pará State, where, probably, the epidemiological profile of disease is associated with the large distances that women in river communities have to travel to perform this test free of charge, the type of economic activity in the region, the local bias still exists with the test, and the degree of difficulty of implementing effective return of patients to medical appointments after obtaining the test result and the same routing for molecular diagnosis of positive cases for type lesions ASC-H and CIN I, II and III.
Acesso aberto (Open Access)
Efeito citoprotetor e cicatrizante gástrico do extrato padronizado de Euterpe oleracea Mart.
(Universidade Federal do Pará, 2024-05) SOUZA, Keyla Rodrigues de; MELLO, Vanessa Jóia de; http://lattes.cnpq.br/9437589201689717
A gastric ulcer is an acidic peptic lesion of the digestive tract resulting from an imbalance between the factors that damage the mucosa and those that protect it. It is a prevalent disease throughout the world and the medications used to treat it, although efficient, have side effects. Among these, açaí (Euterpe oleracea Mart.), has high antioxidant and anti-inflammatory capacity due to its composition of bioactive phytochemicals that include the class of anthocyanins, proanthocyanidins, and other flavonoids with promising health effects. The present work investigated the cytoprotective and gastric healing activity of the standardized extract of Euterpe oleracea Mart. (EO). Initially, the ability of EO to promote increased cell migration of epithelial-type cells (Vero) in the in vitro healing model was evaluated. In the spectrum of evaluation of in vivo antiulcer activity, initially, the cytoprotective activity of EO was determined in gastric ulcer models induced by ethanol and indomethacin. Furthermore, the action of EO on gastric secretion was investigated. The in vivo healing effect was evaluated in a gastric ulcer model induced by acetic acid. Treatment with EO at a concentration of (1 μg/mL) promoted a significant increase in cell migration after 48 hours. Pre-treatment with EO at doses of (2.5 μL/g and 10 μL/g) reduced the area of gastric lesions in ulcer models induced by ethanol and indomethacin. EO was not able to increase pH and reduce acidity or volume of gastric secretion to levels similar to animals treated with omeprazole (20 mg/kg) in a pylorus ligation model. In the gastric ulcer model induced by acetic acid, treatment with EO at doses of (2.5 μL/g and 10 μL/g) for eight days reduced the area of the acid-induced gastric ulcer, increasing the healing rate when compared to animals without treatment (one way ANOVA, post-Tukey test p < 0.0001). EO treatment in the acetic acid model also increased catalase activity, increased total glutathione levels, and reduced malondialdehyde and nitrite levels compared to untreated animals. According to the results, the standardized extract of Euterpe oleracea Mart. (EO) showed a healing effect in both in vitro and in vivo studies. It presented a cytoprotective effect that is probably not related to a capacity to modulate gastric secretion, but possibly related to the reduction of oxidative stress and its healing effects.
Acesso aberto (Open Access)
Efeito da temperatura e molaridade na avaliação das atividades antimicrobiana, citotóxica e antioxidante do bio-óleo da semente do açaí (Euterpe oleracea, Mart.)
(Universidade Federal do Pará, 2024-08) SILVA, Iago Castro da; MACHADO, Nélio Teixeira; http://lattes.cnpq.br/5698208558551065; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Açaí, a fruit from the Amazon, is valuable both economically and nutritionally. Its seeds, which are typically discarded, can be converted into bio-oil through pyrolysis (a process of thermochemical degradation of residual biomass), offering a sustainable alternative to fossil fuels. This study explores how temperature and molarity with Potassium Hydroxide (KOH) and Hydrochloric Acid (HCl), which are chemical impregnation reagents in the process, affect the antimicrobial, antioxidant, and cytotoxic activities of the produced bio-oil. Tests were conducted using Gas Chromatography coupled with Mass Spectrometry (GC-MS) and assays to evaluate antimicrobial, antioxidant, and cytotoxic activities at different temperatures (350, 400, and 450 °C) and molarities (0.5 M, 1.0 M, and 2.0 M). Phenolic compounds were the most abundant in the bio-oil (55.70%), followed by cyclic and aromatic hydrocarbons (11.89%) and linear hydrocarbons (9.64%). Despite a reduction in oxygenated compounds, the bio-oil retained bacteriostatic activity against Escherichia coli and Staphylococcus aureus across various temperature ranges, with notable effectiveness at 350 °C. Antioxidant activity was highest at 350 °C and at lower molarities. Furthermore, lower concentrations of acidic impregnation exhibited cytotoxic effects at high temperatures. Thus, bio-oil from açaí seeds generated through pyrolysis shows potential for antioxidant and antimicrobial activities, suggesting feasibility for further testing in dilutions with lower cytotoxicity.
Acesso aberto (Open Access)
Efeito do óleo da espécie vegetal Caryocar villosum em linhagem de células vero in vitro
(Universidade Federal do Pará, 2024-08) LOPES, Izabella Carla Silva; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
Fibroblasts are cells that participate in different processes in the body, being indispensable in the development and homeostasis of tissues. They are important agents in the healing process, being present in the inflammatory, proliferative and remodeling phases. These cells produce biomolecules that constitute the extracellular matrix, such as collagen, which provide the necessary support for healthy healing. However, healing is a complex process, and it is proneto failure, so it´s important to investigate therapeutic alternatives to produce more effective treatments in cases where natural healing is not effective. Natural products from plants are widely used as therapeutic forms for healing considering their lower side effects, low cost, this combined with traditional knowledge makes it attractive to studies that prioritize valuing biodiversity. Caryocar villosum (Cv), a fruit native to the Amazon region, is a remarkable source of bioactive compounds with therapeutic potential that has cosmetic and pharmaceutical applications. In this work, the action of Cv oil (CvO) on VERO cell line (fibroblast-like cells)was investigated. The cells were treated with 75, 125 and 250 μg/mL for 24 hours. Cytotoxicity assays, optical microscopy, cell proliferation, morphological analysis, and analysis of extracellular matrix components, such as phalloidin staining and immunofluorescence for type III collagen antibody, were performed. Any cytotoxicity was observed in the cells after CvOtreatment. CvO treatment induced morphological and physiological changes in the cells indicating cell activation. Fluorescence microscopy revealed greater cell spreading, rearrangement of actin filaments and increased cell surface exposure compared to untreated cells. Furthermore, this study suggests that fibroblasts treated with CvO are activated through cytoskeletal rearrangement, increasing cell surface, proliferating, and increasing collagen synthesis. These findings indicate that CvO may be a good therapeutic strategy from biodiversity to stimulate the healing process.
Acesso aberto (Open Access)
Efeitos citotóxicos e mecanismo de ação da eleuterina isolada de Eleutherine plicata em modelo in vitro de células c6
(Universidade Federal do Pará, 2024-05) SHINKAI, Victória Mae Tsuruzaki; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
Glioblastoma multiforme (GBM) is the most prevalent malignant primary tumor of the central nervous system (CNS). GBM cells are characterized by rapid proliferation and aggressive migration. There is growing demand for new therapies to treat this tumor, due to current therapeutic limitations. Quinone derivatives from plants have received increased interest as potential antiglioma drugs due to their diverse pharmacological activities such as inhibition of cell growth, inflammation, tumor invasion and promotion of tumor regression. The herb Eleutherine plicata, popularly known as Marupazinho, is widely used in popular medicine due to its pharmacological properties, containing quinone derivatives, more specifically naphthoquinones. Previous studies have demonstrated the antiglioma activity of Eleutherine plicata, which is related to three main naphthoquinone compounds – eleutherine, isoeleutherine and eleutherol – but mechanism of action remains unclear. Thus, the objective of this study was to investigate the potential cytotoxic and antiproliferative effect of eleutherin in an in vitro model of glioblastoma (C6 lineage). In vitro cytotoxicity was assessed by the MTT assay; Morphological changes were assessed by phase contrast microscopy. Apoptosis was determined by the annexin V-FITCpropidium iodide assay, and antiproliferative effects were assessed by the colony formation assay. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The results obtained indicated that eleutherin, isolated from the Hexanic fraction, had a cytotoxic effect on the C6 lineage. Structural changes were observed by image capture, with a significant reduction in colony formation, induction of apoptosis, inhibition of pAKT and reduction in telomerase expression after treatment. Thus, our study showed that the eleuterin molecule has cytotoxic activity in C6 lineage glioma.
Acesso aberto (Open Access)
Exposição à concentração subletal de metilmercúrio: genotoxicidade e alterações na proliferação celular
(Universidade Federal do Pará, 2015-04-01) MALAQUIAS, Allan Costa; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Mercury is a metal that stands out from the rest for present liquid under normal temperature and pressure. This xenobiotic is the largest source of pollution in many parts of the world and has been characterized toxic to the central nervous system (CNS). After dumping in liquid form directly into soil and riverbed, this heavy metal complex with various organic elements or it is converted to methylmercury (MeHg) by aquatic microbiota. The MeHg can move up the food chain, an event known as biomagnification, which directly affects human life. Thereby, the Amazon stands out for having all the components necessary for the maintenance of biogeochemical cycle of mercury as well as populations chronically exposed with this heavy metal. And this metal is considered a public health problem. It is well known that this xenobiotic after acute exposure to high doses promotes disorders related to the emergence of degenerative processes in the CNS, however, the effects at low concentrations are not yet fully described. Despite this cell type play an important role in the mercury intoxication process, the role of this metal on glial cells is not well known, especially on the genome and cell proliferation. Thus, this study aimed to evaluate the effect of exposure to this xenobiotic at low concentration on DNA and cell proliferation in C6 glial lineage cells. The biochemical (mitochondrial activity - measured by MTT assay -) and morphofunctional evaluations (membrane integrity - measured by the assay with dyes and AA BE -) confirmed the absence of cell death after exposure to heavy metals in a concentration of 3 μM for 24 hours. Even without causing cell death processes, the treatment with sublethal concentration of MeHg that was able to significantly increase the levels of markers of genotoxicity (DNA fragmentation, micronuclei, nuclear nucleoplasmic bridges and nuclear bud). At the same time, it was possible to observe a change in the cell cycle by increasing the mitotic index and a change in the cell cycle profile with increased cell population in S and G2 / M phases, suggesting an arrest cell cycle arrest. This change in cell cycle caused by MeHg exposure was followed by number of viable cells and cell confluence decrease, 24 hours after the withdrawal of MeHg of culture medium. The C6 cell line culture in addition showed an increase on doubling time parameter. This study demonstrates for the first time exposure to methylmercury low and sublethal concentration can promote genotoxic events and disturbances in cell proliferation in glial cell origin.
Acesso aberto (Open Access)
A intensificação do comportamento tipo ansiedade induzido por cafeína em Daniorerio(zebrafish) é prevenida pelo tratamento com α-Tocoferol e L-NAME
(Universidade Federal do Pará, 2015-01-23) CARVALHO, Tayana Silva de; OLIVEIRA, Karen Renata Matos; http://lattes.cnpq.br/3032008039259369; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
The growing consumption of beverages with high caffeine content can result in the appearance of symptoms from anxiety disorder induced by this drug. Currently, it has been used as a pharmacological caffeine inductor anxiety-like behavior and this induction may help facilitate better understanding of the relationship between behavioral changes and the mechanisms involved in this effect. Therefore, this study proposed that the nitrergic pathway could be a key mechanism to explain the behavioral effects produced by caffeine and that these effects could be reversed by an antioxidant, hence, the present work we had to evaluate the possible effect of L –NAME and - tocopherol expanded in anxiety-like behavior by caffeine in light/dark preference (LDP) test and novel tank dividing (NTD) test in Daniorerio. Zebrafish fish species (N=178) used were divided into the following experimental groups: SAL - 0.9% saline; CAF - Caffeine 100 mg/kg; DMSO - dimethylsulfoxide 0.1% ; L-NAME - (N -nitro -L - arginine methyl ester hydrochloride) 10 mg/kg; TF - -tocopherol 1 mg/kg (received only one injection by i.p.); SAL + SAL; DMSO + SAL; SAL + CAF , L-NAME + SALT , L-NAME + CAF ; TF + CAF, received two followed injections, one injection of each substance in the form of co-treatment, by i.p. The animals were submitted to the light/dark preference test and novel tank dividing test. All tests were filmed and the videos were evaluated using X-PLO-RAT. Data were expressed as mean ± SEM. The normality test was applied using the Shapiro-Wilk test and the ANOVA parametric test one-way with Tukey post-hoc, with the significance level set at p<0.05. The - tocopherol at a dose of 1 mg/kg, reversed all anxiety-like behavior parameters expanded by caffeine in LDP and NTD tests and this effect was similar to that observed when given one inhibitor of the enzyme nitric oxide synthase (NOS), L- NAME. Therefore, this study first demonstrated that the behavioral effect magnified by caffeine in scotaxis test and DVN test can be modulated by the nitrergic pathway and that the -tocopherol reverses completely this anxiety-like behavioral effect induced by caffeine.
Acesso aberto (Open Access)
Monitoramento das reações adversas ao novo tratamento da tuberculose
(Universidade Federal do Pará, 2016-05-22) RODRIGUES, Miguel Wanzeller; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
Tuberculosis is an infectious disease that despite the effective prophylactic and therapeutic resources is one of the most serious problems of global public health. In 2014, there were 67,966 new cases of the disease in Brazil, with the highest incidence rate in the states of Amazonas, Rio de Janeiro, Acre, Pernambuco, Mato Grosso and Pará. Three factors contribute to continuity of tuberculosis in Brazil: the HIV pandemic the development of multiresistant strains and failure of BCG. The lack of adherence to treatment is one of the main reasons the spread of resistance. In order to reduce this problem and minimize adverse reactions, WHO in 2006 recommended a new regimen: 2RHZE (intensive phase) and 4R (maintenance phase), which was adopted by Brazil in 2010. However, adverse reactions requiring discontinuation of treatment has not been estimated with the new regimen, which justifies this study aimed to analyze the occurrence of adverse events in subjects with tuberculosis in the use of new treatment regimen (Isoniazid, Rifampin, Ethambutol, Pyrazinamide). A prospective longitudinal study of 57 subjects with clinical diagnosis, laboratory and radiological tuberculosis. The renal function tests (urea and creatinine) and liver (AST, ALT, alkaline phosphatase, bilirubin and gamma GT) were performed every month of treatment. In the study, Disease affected more males with low education, who used tobacco and alcohol and regardless of age. There were increasing urea values in the last two months of treatment, but creatinine was normal during treatment. Regarding the assessment of liver function, fluctuations were observed in biochemical parameters analyzed, but remained in the normal range. It is noteworthy that a subject has developed framework of cholestatic liver disease, which resolved upon discontinuation of treatment. Early diagnosis, coupled with immediate treatment enables the patient an effective outcome in the fight against tuberculosis, as it keeps the biochemical parameters without major changes, allowing for a better adherence and clinical improvement of the patient.
Acesso aberto (Open Access)
Novas ferramentas terapêuticas contra a convulsão e o comportamento tipo depressivo: ensaios pré-clínicos com açaí clarificado
(Universidade Federal do Pará, 2016-09-28) MONTEIRO, José Rogério Souza; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Açai (Euterpe oleracea Mart.) Is a typical northern palm of Brazil, rich in phenolics and anthocyanins, substances with high antioxidant activity, anti-inflammatory and proven beneficial health effects. Oxidative stress and inflammation are involved in the generation and propagation of seizures, main clinical feature of epilepsy, and in the pathogenesis of depression. In this work we investigated the potential neuroprotective effect, anticonvulsant and antidepressant commercial samples of clarified açaí (CA). Only four doses of CA were enough to increase latencies for myoclonic and tonic-clonic seizures and to reduce the total duration of tonic-clonic seizures induced Pentylenetetrazole (PTZ). Eletrocorticográfics changes induced by PTZ were prevented significantly by CA. In the depressive-like behavior model induced by lipopolysaccharide (LPS), CA decreased immobility time and increased significantly the sucrose consumption of animals, indicating that the CA has preventive activity on the appearance of behaviors which are characteristic of clinical depression. Both the PTZ model as LPS CA exhibited potent preventive activity against the oxidative stress. CA prevented lipid peroxidation and elevated nitrite levels in the cerebral cortex, hippocampus, striatum and prefrontal cortex. These results demonstrate for the first time that acai is a fruit that exerts potent protective activity against the development of seizures, the depressive-like behavior and oxidative stress, which is an additional protection for individuals who consume this fruit.
Acesso aberto (Open Access)
Papel do óxido nítrico na infecção malárica por P. gallinaceum
(Universidade Federal do Pará, 2013-10-08) OLIVEIRA, Karla Caroline Marques de; MACCHI, Barbarella de Matos; http://lattes.cnpq.br/5330351659478942; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Malaria is a severe infectious disease caused by parasites of the genus Plasmodium that infect different types of vertebrate’s hosts and is responsible for a huge number of deaths. The severe Malaria can lead to death and involves different pathophysiological signs as well as anemia and inflammation. Experimental models are necessary to improve the knowledge about mechanisms involved at the pathogenesis of the disease and the developing new protocols of treatment. Chickens infected with P. gallinaceum are a good model of malaria due to phylogenetic relatedness with human Plasmodium and because both species presents common clinical signs as cerebral malaria. The Nitric Oxide (NO) is an important effector molecule, but little is known about their role in malaria on chickens, meanly due to the lack of specific markers to evidence the NO production in this model. It is known that chickens infected with P. gallinaceum has a high mortality and causes an overproduction of nitrite by macrophages. The animals, when treated with aminoguanidine (AG), an inhibitor of inducible oxide nitric synthase (iNOS), showed a higher level of parasitemia. However, the rate of survivor was superior, beyond the clinical manifestations, as milder anemia. It is necessary to achieve a better comprehension about physiological aspects of avian malaria with the inhibition of NO’s production by the AG. In the context , the present study aims to investigate NOS activity and the role of NO during the avian malaria infection, with in vivo models, using P. gallinaceum as pathological agent , and in vitro with chicken’s macrophage of HD11 strain. This research will give a better understanding of avian malaria in chickens, including cerebral, and the involvement of nitrergic system in infected chickens.
Acesso aberto (Open Access)
A sinalização adenosinérgica na regulação da gravidade da sepse e da liberação de armadilhas extracelulares de neutrófilos (NETs)
(Universidade Federal do Pará, 2024-09) PAMPOLHA, Ana Flavia Oliveira; CUNHA, Fernando de Queiroz; http://lattes.cnpq.br/2869737621338203; HTTPS://ORCID.ORG/0000-0003-4755-1670; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Neutrophils express different purinergic receptors, including four adenosine-ligand P1 receptors, which regulate their primary functions, such as migration and production of inflammatory mediators, including neutrophil extracellular traps (NETs). In sepsis, NETs exhibit a dual role: microbicidal properties but also contribute to organ damage, leading to multiple organ failure and worsening the clinical condition. In this study, we investigated the role of adenosine in NETs release and the progression of experimental sepsis induced by the Cecum Ligation and Puncture (CLP) or endotoxemia models. We observed that treatment of mice subjected to both models with adenosine deaminase (ADA), which metabolizes adenosine to inosine, aggravates organ damage and reduces the survival rate of septic animals. Supporting these findings, we demonstrated that NET production in vitro by neutrophils stimulated with PMA was enhanced by ADA treatment and reduced by NECA, a molecule that mimics adenosine's actions. The modulation of NET production by adenosine was attributed to the activation of A2AAR receptors. In conclusion, our results suggest that during sepsis, adenosine is released and decrease NET production via A2AAR activation.