Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375
O Mestrado 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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Item Acesso aberto (Open Access) Alterações de expressão gênica na linhagem de glioblastoma humano U87 após exposição ao MeHg e HgCl2(Universidade Federal do Pará, 2016-12-02) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468The organic and inorganic forms of mercury have been pointed as important contaminants in several world regions due to its toxicological characteristics. Various studies have reported that the intoxication by methylmercury (MeHg) and mercury chloride (HgCl2) can lead to central nervous system impairment. It is generally agreed that glial cells are important for the mechanisms responsible for cellular protection against the damages caused by the mercury. However, little is known about the influence of the mercury in the cells genome. Hence, in the present study we did a complete mapping of the humam glial cells genetic network after mercury exposition with the aim to indentify the possible genetic alterations that occurred via the organic and inorganic forms of mercury. Our results demonstrated that U87 lineage cells are more sensitive to MeHg exposition when compared with HgCl2 exposition. Using an analysis of the concentration curves the LC50 was obtained from 28.8μM and 10,68μM after 4h and 24h exposition to MeHg and a LC50 of 92.25μM and 62.75μM after the same time periods exposition to HgCl2. Regarding the genic pool, our results have shown that both metal forms led to alterations in the genic dosage where the MeHg exposition was highly influenced by the concentration and time, whereas the HgCl2 exposition seemed have been strongly influenced by the exposition time. In total there were 205 indentified genes with a lower genic dosage and 188 genes with elevated expression, (Fold change > 5) after 4h exposition and 5μM of MeHg, and 204 down-regulated genes; and 180 up-regulated genes after HgCl2 exposition in the same concentration. The analysis after 24h exposition showed 90 down-regulated genes and 3 up-regulated genes after 1μM of MeHg; 116 genes were down-regulated and 66 genes were up-regulated after a 10μM exposition of MeHg. As for the HgCl2, there were 98 down-regulated genes and 73 up-regulated genes for the groups exposed to 5μM of HgCl2; 326 down-regulated genes and 66 up-regulated genes for the groups exposed to 62,75μM of HgCl2. Our dataset suggests that both mercurial forms are able to alter the cell genetic expression profile thus interfering in important signaling paths prone to gives rise to biochemical impairments and glial cells phenotypes.Item Acesso aberto (Open Access) Análise imunológica e genotóxica em Rattus Novergicus da linhagem wistar tratados com ciclofosfamida(Universidade Federal do Pará, 2016-08-11) CARVALHO, Heleniana Maria Miranda de; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099The development of this work has given up due to the need to better understand the immune system, taking into account the diversity of experimental immunosuppression models as well as the variety of immunological responses and genotoxic differences these, related species, the drug and doses used. Thus, aim of this study was to analyze the effects on the immune system and genotoxic effects in Rattus norvegicus Wistar, after inoculation of the alkylating agent cyclophosphamide (CY). The administration of 50 mg / kg in rodents CY, possible to observe a significant decrease in the parameters of cellularity and relative weight of lymphoid organs. The humoral immunity of rodents has undergone deletion, since the analysis of the antibody titration was performed on the test plate forming cells and hemolysis testing. four inoculations that immunosuppressant and the intervals between the inoculations was determined by recovery of normal levels of the above parameters were performed. Both times the drug was administered, there was a reduction in the number of lymphocytes and neutrophils subsequently decreased, but only the second contact CY was observed immunosuppression. The analysis of the genotoxicity of cyclophosphamide (CY) was analyzed using the comet assay and was of paramount importance because dectamos genomic damage occurring in DNA exposed to different doses of cyclophosphamide (CY), which were 50 mg / kg in the first two phases and 25 mg / kg during the last two phases of the experiment. Furthermore, it was found that the genotoxic effects are cumulative with each CY dose applied, because even being administered in the third phase, the middle concentration (25 mg / kg) of the two inoculations initial CY the damage index does not correspond to half damage indices of the first and second vaccination. However, the analysis and immunologically genotoxicamente rodents, our work will enable testing new therapeutic immunosuppression regimens.Item Acesso aberto (Open Access) Avaliação neurocomportamental da exposição crônica ao Mercúrio inorgânico na memória social e memória emocional de ratos wistar machos adultos(Universidade Federal do Pará, 2015-02-20) FERNANDES, Rafael Monteiro; SILVA, Márcia Cristina Freitas da; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468Inorganic mercury is easily absorbed by ingestion or cutaneous. However, a relatively small amount of Hg2 + crosses the blood brain barrier or biological membranes, and in adult rats, the retrograde axonal transport only way to Hg2+ uptake by neurons, presenting great potential neurotoxic. The aim of this study was to determine the effects of chronic exposure to mercury chloride in social and emotional memory in adult rats. For this we used male Wistar rats (n= 40) with 5 months of age , divided into two groups , one of which was exposed to mercury chloride (HgCl2) by intragastric gavage (0,375mg / kg) for 45 days. The other group, called the control group (n=20) received distilled water by gavage. The following behavioral tests were used: the open field test, social recognition test for the evaluation of social memory; the elevate T maze test (LTE) was used to assess learning in the state of avoidance and short and long - term memories. After completion of the tests, the animals were sacrificed to evaluate the level of total mercury in the hippocampus by an Atomic Absorption Spectrophotometer. The results showed that animals subjected to exposure to mercury chloride did not show deficits in exploration activity. The data from social recognition test, showed that there was no change in social memory. In LTE test, the group exposed to HgCl2 required a greater number of exposures for the acquisition of avoidance criteria (p<0.05) and a higher latency in the open apparatus arm (p<0.05). After 24 hours, it was found that treated animals spent less time in the closed arms than in the control group, suggesting the long-term memory deficits. By just watching the HgCl2 group, noticed an improvement in the retest, indicating preservation in the short-term memory. The data of atomic absorption spectrometry showed greater deposition of mercury in the hippocampus of affected animals, as compared to control animals.Item Acesso aberto (Open Access) Avaliação seriada do perfil hematológico e bioquímico de primatas não humanos da espécie Sapajus apella tratados com lde-oleato de paclitaxel como instrumento para a terapêutica do câncer(Universidade Federal do Pará, 2017-02-23) OLIVEIRA, Nayara Cristina Lima de; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099Study of a chemotherapy delivery system, called LDE, with lipid composition similar to the natural low density lipoproteins of the body, denominated by the acronym LDL. LDEs have advantages over commercial chemical forms, since it is able to concentrate in the neoplastic tissues after injection into the circulatory chain, thus being able to target the tumors. LDE can be used as a "carrier" of paclitaxel (PTX) for possible reduction of toxicity and increase of its therapeutic action. The use of non-human primates as in vivo experimental models are of great importance in human health applications due to their anatomical, biochemical and phylogenetic similarities with human primates, generating results that can be interpreted more closely and safely to The phenomena in humans. The aim of the project was to evaluate the chronic toxicity of nanoparticles associated with to chemotherapy Paclitaxel (LDE-PTX) in individuals of the Sapajus apella species, based on the determination of hematological and biochemical parameters and their possible alterations. During the research 15 animals were used, divided into groups: Negative control (CN); Experimental (EXP1 and EXP2) where the animals received LDE-PTX intravenously two different doses of 175 mg / m2 and 250 mg / m2 respectively; and positive control (CP1 and CP2) where the animals intravenously received the drug in commercial form at the same doses used in the experimental group, respectively. Primates were accompanied for 6 cycles of chemotherapy, with interval of 3 weeks. Hematological and biochemical analysis was performed at each cycle through erythrogram and leukogram, alkaline phosphatase, total protein, albumin and globulin, total bilirubin and fractions, glycemia, amylase and serum lipase. E of the sodium and potassium eletrolytes were carried out in the serum of the animals during the collection days. Data were expressed as mean ± standard deviation and submitted to analysis of variance ANOVA, with Bonferroni post-test with significance for p <0.05, through BioEstat®5.3. The obtained results demonstrated advantages of the use of LDE-PTX, since the hematological tests demonstrate that there was a lower toxicity in all the chemotherapeutic cycles and the non-alteration of the majority of the biochemical parameters, demonstrate that the toxicity of the tested drug associated to LDE present smaller Effect toxic than its commercial version. It was concluded from the analysis of the results that hematological and biochemical toxicity was lower in treatment with PTX associated with LDE than treatment of PTX in its commercial form.Item Acesso aberto (Open Access) Caracterização das alterações no córtex motor de ratos adultos submetidos à exposição crônica com mercúrio inorgânico(Universidade Federal do Pará, 2016-12-12) TEIXEIRA, Francisco Bruno; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468Mercury is a highly toxic heavy metal, which can be found in organic and inorganic elemental forms in the environment. The inorganic mercury has lower liposolubility and consequently, lower absorption in the body, and lower passage through the blood brain barrier. For this reason, exposure models using inorganic mercury in rats to evaluate its effects in the central nervous system are rare, mainly in adults. Therefore, we investigate the potential of low concentration of mercury chloride (HgCl2), in a chronic exposure model to promote motor changes associated to variables in the oxidative balance, cellular cytotoxicity and apoptosis in the motor cortex of adult rats. For this purpose, rats were exposed for 45 days to a dose of 0.375 mg/kg/day. After this period, the animals were submitted to motor evaluation and then were collected for measurement of total deposited mercury in neural parenquima, assessment and quantification of cellular cytotoxicity and apoptosis and evaluation of the oxidative balance. Furthermore, animals were perfused to evaluate the density of mature neurons and astrocytes of the motor cortex. It was observed that chronic exposure to inorganic mercury decreased balance and fine motor coordination. In addition, we found that this exposition model led to cytotoxicity and cell death by apoptosis, formation of deposits of mercury and oxidative stress evidenced by the increase of lipoperoxidation and the concentration of nitrites and decrease in total antioxidant capacity. Thus, our results provide evidence that a exposition to inorganic mercury, even before his lower capacity to cross the biology barriers, It is still capable to inducing motor changes associated to cell death and apoptosis and oxidative stress in the motor cortex of the adult rats.Item Acesso aberto (Open Access) Dislipidemias e síndrome metabólica em populações expostas ao mercúrio: estudo observacional de coorte nas regiões do rio Tapajós e Tucuruí(Universidade Federal do Pará, 2016-09-30) CAMPOS, Núbia Fernanda Santos da Silva; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265Cardiovascular diseases have emerged as the leading cause of death in Brazil and in the world, representing a third of the deaths and the main spending on health care. Between 2000-2010, the number of deaths from cardiovascular disease in one hundred thousand inhabitants increased by 28% in the North, with dyslipidemia and metabolic syndrome among the main risk factors. These values become more worrying as it may be underestimated because of consequential underreported the geographical isolation of the region, which is characteristic of northern Brazil. Dyslipidemias correspond to changes in the plasma lipid profile, and represents a criterion for the diagnosis of metabolic syndrome. Metabolic syndrome can be defined as a set of metabolic changes such as hyperglycemia, dyslipidemia, hypertension and obesity. Recently, animal studies and clinical models have shown increased risk of atherosclerotic disease and hypertension with exposure to mercury. In the Tapajós River region, several studies have shown human exposure in riverine populations that consume fish contaminated with methylmercury. Also, recent data from our group show that the riverine communities of Tucuruí have high levels of mercury. The aim of this observational cohort study was to analyze the possible lipid abnormalities and the presence of metabolic syndrome in riverside communities in the Amazon region: Boa Vista do Tapajós, Barreiras, Pimental, Brasilia Legal, Fordlândia and Pedra Branca (Tapajós), Vila Cametá and community Ouro Verde (Tucuruí) with mercury exposure history. For this, the calculations were carried out in body mass index (by weight and height), blood pressure measurements, analysis of glycemic control (fasting blood glucose) and lipid, by plasma levels of triglycerides, total cholesterol, HDL and the calculations LDL, VLDL and HDL cholesterol did not the lipid. After application of the inclusion and exclusion criteria, a total of 337 adults of both sexes (220 of the Tapajos and 117 Tucuruí) were analyzed. High average levels of obesity and high frequency of individuals who had dyslipidemia were detected, especially in Tucuruí, where the frequencies were even higher than in the Tapajos. Also, high percentages of individuals were identified with metabolic syndrome (14% to 35% depending on the definition adopted). The criteria adopted by the NCEP have proved the most sensitive for the identification of metabolic syndrome (MS) in these populations. The main factor that contributes to the detection of the presence of MS was the low HDL level, present in 32% of individuals with MS. In Tapajós, the second and third most common factors were the high levels of triglycerides and glucose, however in Tucuruí was altered blood pressure and high triglycerides levels. In conclusion, our study provides, epidemiological data on the prevalence of dyslipidemia, overweight and obesity, high blood pressure and metabolic syndrome in adults bordering the Amazon. Adding to this, the epidemiological assessment of the lipid profile is an important tool for the promotion of health measures to prevent and reduce cardiovascular risk factors.Item Acesso aberto (Open Access) Efeito do metilmercúrio em girinos e recém-metamorfoseados de Physalaemos ephippifer (Steindachner, 1864) (Anura, Leptodactylidae)(Universidade Federal do Pará, 2016-11-23) CASTELO BRANCO, Ailin; BAHIA, Verônica Regina Lobato de Oliveira; http://lattes.cnpq.br/1218901740124657; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649The metal contamination in amphibians has been taken into account as one of the factors contributing to the population decline of these animals. The mercury (Hg) is an environmental contaminant showing high levels of toxicity. Its organic form, methylmercury (MeHg), may bioaccumulative reaching high levels in the trophic chain. For amphibian populations, bioaccumulation of metals is important once that such animals may be MeHg diffusers from the aquatic environment to the terrestrial environment because of their double life cycle. MeHg concentrations in high doses can cause obvious lethargic effects and larvae mortality of amphibious, however little is known about subchronic effects of MeHg doses. Therefore, the present research aims to explore the effects of subchronic exposure to MeHg in one experimental model, the species Physalaemus ephippifer, describing, identifying and characterizing the possible changes in physical performance of larvae and newly metamorphosed, in addition to teratogenic and morphological changes in the sensory and nervous system. After the toxicological test, with MeHg concentrations of 0.007 μg/ml, 0.004 μg/ml 0.0007 μg/ml and 0.0004 μg / ml and negative control, the animals were assessed by behavioral analysis simulating breakout predatory, morphometric and analysis in light microscopy and scanning electron microscopy. Our results revealed that MeHg concentrations did not induce locomotor weaknesses in tadpoles and nor apparent anatomical morphological damage, however, it induces the appearance of a massive cell count of pyknotic nuclei in the areas of the cerebellum and optic tectum. Such alteration, which remains in the animal even after metamorphosis, induces a locomotor weakness in concentration of 0,007μg/ml which is also the concentration where one increased teratogenic damage effect (corneal malformation) is observed. Therefore, we conclude that MeHg is a neurotoxic and teratogenic agent for P. ephippifer and that such features lead to one decrease in locomotor performance. The present work may contribute to the knowledge on effect of MeHg in amphibian populations that live in environments where this contaminant is present as member of the ecosystem.Item Acesso aberto (Open Access) Investigação dos efeitos protetores do selenito de sódio sobre a neurotoxicidade do metilmercúrio em diferentes períodos de desenvolvimento de ratos wistar(Universidade Federal do Pará, 2011-12-28) SANTOS, Nilton Barreto dos; COSTA, Edmar Tavares da; http://lattes.cnpq.br/6776869402973569; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306Exposure to mercury compounds results in oxidative damages, seriously affecting the central nervous system both in humans and in experimental models. We used Wistar rats at different stages of neuro-development in order to investigate potential protective effects of selenium (sodium selenite) in an in vivo model of exposure to methylmercury (MeHg). Subjects (age groups P1 and P21) were given lactational and orally, respectively: vehicle, Selenium (5ppm), MeHg (10 ppm) or selenium (5 ppm) plus MeHg (10 ppm) for 20 and 10 days respectively (n = 8 per group). After treatment, the rats were submitted to the following behavioral tests: open field and Morris water maze to examine motor deficits and memory/learning, respectively. After intracardiac perfusion we performed immunohistochemistry for Neu-N. In order to evaluate possible deleterious effects in neuronal populations, we counted neurons in the hippocampus (polymorphic layer). As a result, we found significant reduction in locomotor activity of neonates (P1) when exposed to MeHg. Besides, groups exposed to MeHg (alone or in association with selenium) showed learning/memory deficits. P21 animals treated with MeHg showed increase in locomotor activity, effect abolished by concomitant administration of selenium. When submitted to water maze, only subjects in the control and selenium groups showed reduction of the time latency. As assessed by stereological counting, we noticed reduction in the number of hippocampal neurons only in P21 animals exposed to MeHg. Combined, our results showed that MeHg exposure produces age-dependent behavioral effects. Also, despite other findings in the literature, under our experimental conditions administration of selenium was only able to interfere with motor deficits in older animals, besides not being able to interfere with memory/learning deficits nor the MeHg-induced neuronal death. Possible mechanisms associated with these partial protective properties of selenium in the later stages of neural development have yet to be elucidated.Item Acesso aberto (Open Access) Metilmercúrio e mercúrio inorgânico em peixes comercializados nos mercado municipal de Itaituba (Tapajós) e mercado do Ver-o-peso (Belém)(Universidade Federal do Pará, 2011-12-12) ARRIFANO, Gabriela de Paula Fonseca; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265Mercury is a dangerous metal and an important source of environmental contamination in Brazil and particularly in the Amazon. The main target organ of this metal is the CNS where it causes damage that can lead to classic symptoms: ataxia, paresthesia, dysarthria, and changes in the developing nervous system of children. The mercury contamination in the Amazonian rivers increases the amount found in fish, especially those at the top of the food chain, exposing people to mercury poisoning the rivers, since the fish is a central element in the diet of these populations. Therefore, it is essential periodic monitoring of mercury levels in fish species consumed in the region. Our study proposes to identify the levels of methylmercury and inorganic mercury in fish species consumed by the riverside populations of the Tapajós region and compare them with the levels found in the same species obtained in the region of Belém also perform a comparison with results obtained by Dos Santos et al. (2000) and analyzing the current level and the old. Fish were collected in the municipal market Itaituba, Tapajós, and market the Ver-o-Peso in Belém. Muscle samples of each fish were dried and analyzed by the Universidad de Castilla-La Mancha (Spain) for quantification of methylmercury and inorganic mercury. The results obtained in this study showed that only piscivorous fish from the Tapajós region have levels of methylmercury above the limit recommended by WHO (0.5 μg / g). All in all study groups, levels of inorganic mercury are well below this limit. The species was the most contaminated Brachyplatystoma flavicans (Dourada) and even to exceed five times the WHO limit of tolerance. With our data, we can say that the fish of the Tapajós region are still currently exposed to high concentrations of mercury. The non-fish-eating species had low concentrations of organic mercury, is fit for human consumption. This study supports the importance of continued monitoring of the environments considered exposed and not exposed in the Amazon. Knowledge originated by this monitoring definitely foster the development of prevention strategies and government actions before the problem of mercury contamination in the Amazon. Keywords: inorganic mercury, methylmercury, fish, Tapajós, BelémItem Acesso aberto (Open Access) Níveis de mercúrio, prolactina e interleucina 10 em mulheres em idade reprodutiva e puérperas dos municípios de Itaituba e Ananindeua, Pará(Universidade Federal do Pará, 2012-05-02) JESUS, Iracina Maura de; DINIZ, Domingos Luiz Wanderley Picanço; http://lattes.cnpq.br/9601463988942971The ability of interfering in the immunological and endocrine organic systems has been attributed to the mercury (Hg), besides the nervous and renal systems frequently affected by this toxicant agent. Women in fertile age or pregnant constitute a vulnerable group for those effects, in relation to themselves and their fetus. The mercury exposure was assessed as well as the prolactin (PRL) and interleukin-10 (IL-10) levels in 144 women (in the post-partum and about one year later) of Itaituba, area under environmental Hg impact and in women of the metropolitan area of Belém, most of all from Ananindeua, area without known Hg impact (156 puerperal women and 156 non-puerperal). Total Hg (Hg-t) analyses in whole blood were carried out by Atomic Absorption Spectrometry Cold Vapor. Serum analyses of PRL were made by Enzyme Immunoassay with final detection by fluorescence and IL-10 serum analyses were accomplished by Enzyme Immunoassay of Solid Phase. Demographic and epidemiological data were obtained through semi-structured questionnaire. Puerperal women of Itaituba presented average of Hg-t, PRL and IL-10 of 13.93 μg/l, 276.20 ng/ml and 39.54 pg/ml, respectively. Puerperal women of Ananindeua presented respective Hg-t, PRL and IL-10 averages of 3.76 μg/l, 337.70 ng/ml and 4.90 pg/ml. Non-puerperal women of Itaituba presented Hg-t mean of 12.68 μg/l, PRL mean of 30.75 ng/ml and IL-10 mean of 14.20 pg/ml. Mean of Hg-t, PRL and IL-10 in non-puerperal women from Ananindeua were of 2.73 μg/l, 17.07 ng/ml and 1.49 pg/ml, respectively. Levels of Hg-t, PRL and IL-10 were higher in Itaituba (p<0.0001), except in PRL levels of puerperal women, higher in Ananindeua. Similar Hg levels in women of Itaituba in two assessment (p=0.7056) and positive correlation suggest continuity of exposure (r=0.4736, p<0.0001). The main predictor variable of mercury levels was the fish consumption in the linear and logistic multiple regression models. Parity and IL-10 levels were positively associated with PRL in puerperal women of Itaituba while newborn weight and IL-10 levels presented positive association with PRL in puerperal women of Ananindeua. IL-10 was negatively associated with PRL in non-puerperal women from Itaituba (p=0.0270) and positive association in Ananindeua (p=0.0266). Levels of Hg-t showed negative association with PRL in puerperal women and positive association with working in garimpo (p=0.0173) (the last one was also important for non-puerperal women) in Itaituba, according logistic models. IL-10 was positively associated with recent morbidity in puerperal women of Itaituba (p=0.0210), negatively with ingestion of alcoholic beverages (p=0.0178) and positively with working in garimpo in non-puerperal women (p=0.0199). The chronic Hg exposure of women from Itaituba, difference among the Hg, PRL and IL-10 levels in exposed women compared with non exposed group and association with relevant epidemiological variables, suggest the possibility of Hg impacts in the women's immunoendocrine system in Itaituba, calling attention for the health surveillance of this population and the possible use of assessment biomarkers as PRL.