Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390

O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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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)
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)
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.

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