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Acesso aberto (Open Access)
Acidente vascular encefálico isquêmico na exposição crônica ao etanol: estudo pré-clínico da comorbidade e da resposta a minociclina
(Universidade Federal do Pará, 2015-02-27) FONTES JÚNIOR, Enéas de Andrade; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Stroke is the second largest cause of death in the world and the leading in Brazil, with 87% of strokes due to ischemic processes. Chronic ethanol consumption, usually beginning in adolescence, is recognized as an independent risk factor for increased morbidity and mortality by stroke. Although cases combining the two diseases are relatively common, there is no data in animals or clinical models demonstrating the quality or mechanisms of interaction between the two morbidities, nor its impact on therapeutic intervention. Considering the recent studies proposing minocycline as a new therapeutic tool for the treatment of stroke, this study aimed to investigate the interaction between the Chronic Alcoholic Intoxication (CAI) started in adolescence and the stroke in motor cortex of adult rats, and the effects of treatment with minocycline on this interaction, using behavioral, cellular and molecular parameters. Female Wistar rats (35 days-old) were chronically exposed to ethanol (6.5 g/kg/day, 22.5% w/v) or water for 55 days. One day after the end of the CAI focal ischemia was induced in motor cortex with the endothelin-1 (ET-1), followed by seven-day treatment with minocycline or saline. After this period, the animals were assayed with open field and rota rod tests. Immediately, animals were sacrificed and cortex was dissected for evaluation of nitrite and lipid peroxidation levels. In all groups, some animals were perfused and the motor cortex subjected to histological analysis to assess the damage, and immunohistochemical labeling to neuronal death (anti-NeuN), microglial/macrophage (anti-ED1) and astrocytes (anti-GFAP) activation. The ethanol intoxication from puberty to adulthood potentiated the damage caused by stroke, causing major losses in capacity to start and running movements as well as the strength and motor coordination compared to ischemic animals pretreated with water. These manifestations were accompanied by increased neuronal loss, reduced ED-1+ and GFAP+ cells and higher levels of nitrite and lipid peroxidation. Treatment with minocycline was effective in preventing/reverse motor deficits and tissue damage induced by focal ischemia, also inhibiting the increase in oxidative stress markers. The CAI either alone with succeeded by focal ischemia, harmed the outcome of treatment with minocycline. Our results indicate that heavy alcohol intoxication during adolescence exacerbates the motor deficit and tissue damage in animals subjected to focal ischemia. This process appears to be associated with microglia/astroglial activation, but mainly with oxidative stress. It also shows that the previous history of CAI started adolescence interferes significantly in the treatment of cerebral ischemia with minocycline.
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/3512648574555468
The 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.
Acesso aberto (Open Access)
Alterações no comportamento motor e na bioquímica oxidativa de ratas intoxicadas agudamente com etanol no período inicial da adolescência
(Universidade Federal do Pará, 2015-01-30) CERASI JUNIOR, Antonio José; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Ethanol (EtOH) is one of the most commonly psychoactive substances consumed by young people, usually occurring in episodes of binge consumption, which is an intense form of drinking followed by a period of abstinence. In Brazil, the rates of alcohol abuse by female adolescents have increased in the past few years. This population is more sensitive to the neurotoxic effects of this substance since the complete development of structures such as the cerebellum occurs in this stage of life. Acute and chronic consumption of ethanol and its catabolism are associated with motor behavior alterations so as the generation of reactive oxygen species (ROS) and other metabolites. The purpose of this study was to investigate the effects of EtOH exposure following an acute binge pattern in female rats on their early adolescence (n = 20, n = 10 animals per group) received distilled water or EtOH (3 g / kg / day, 20 w / v) by gavage, for 3 consecutive days. Seven and a half hours after the last day of administration, the behavioral tests of spontaneous locomotor activity and rotarod were performed. Subsequently, the animals were sacrificed for cerebellum removal and the oxidative biochemical tests in cerebellar tissue were carried out. Behavioral tests showed that acute binge in rats on early adolescence did not alter spontaneous locomotor activity, but elicited alterations in motor learning. Oxidative biochemical results showed a high activity of catalase, which demonstrates that there was an offset of the body to reverse the ROS production in the cerebellum of adolescent rats acutely exposed to EtOH followed by a withdrawal period (binge).
Acesso aberto (Open Access)
Análise das manifestações emocionais e motoras de ribeirinhos expostos ao mercúrio na Amazônia
(Universidade Federal do Pará, 2016-02-19) COSTA JUNIOR, José Maria Farah; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; PINHEIRO, Maria da Conceição Nascimento; http://lattes.cnpq.br/6353829454533268
Introduction: The investigation of impacts clinico-neurological associated with exposure to mercury levels in exposed populations are necessary in the Amazon. Objective: To analyze the emotional and motor manifestations of riparian exposed by diet in the municipalities of Itaituba/PA and Acara/PA. Method: Hair samples were collected for the determination of total Hg, obtaining of demographic data and emotional symptomatology (depression, anxiety and insomnia) and motors (paresthesia, muscle weakness, imbalance when walking, tremor, pain in the limbs and dysarthria). Results: There was a prevalence of females in both municipalities, as well as a higher frequency of women of reproductive age. The median concentration of total mercury (HgT) in Itaituba was significantly higher (p <0.0001) than in Acará. The emotional manifestations were identified in 26 (26,5%) participants from Itaituba and in 24 (52,2%) in Acará. With regard to the specific motor complaints in Itaituba occurred in 63 (64,3%) volunteers, with pain in the limbs (36,7%), paresthesia (32,6%) and muscle weakness (27,5%) the most frequently mentioned. In Acara, 33 (71,7%) participants had motor manifestations with the highest number of complaining of paresthesia (54,3%), pain in the limbs (52,2%) and tremor (34,8%). The average concentrations of HgT those with emotional manifestations, with motor manifestations and emotional and motor manifestations were above the considered tolerable (6μg/g) by the World Health Organization in Itaituba Conclusion: The results revealed the influence of the exposure levels about the emotional and motor manifestations. The monitoring with the application of qualitative and/or quantitative conventional specific tests are needed to better support and control cases, as well as the investigation of other clinical signs.
Acesso aberto (Open Access)
Análise de parâmetros de exposição mercurial, suscetibilidade genética e intoxicação em populações ribeirinhas do Tapajós e Tucuruí
(Universidade Federal do Pará, 2016-08-30) ARRIFANO, Gabriela de Paula Fonseca; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Mercury is a heavy metal responsible for intoxications worldwide. Most toxic form is methylmercury that has affinity for the central nervous system, with recognized neurotoxicity. Some regions of the Amazon are well characterized by mercury exposure in humans, as the region of the Tapajos, due to local mining activity, for example. However, others, such as Tucuruí, remain virtually unstudied, with only one study in humans to date. In the Amazon, there is a large number of studies showing mercury exposure, however, intoxication and susceptibility studies are far less numerous in the Amazonian populations, and even today, there is no study analyzing simultaneously the three factors. The objective of this study was to determine the exposure (mercury content in the body by using mercury levels in hair samples), the individual susceptibility (genetic predisposition of each individual to suffer a damage because the exposure, using the genotyping of apolipoprotein E) and the intoxication (quantifying the extent of the damage already caused by using biomarkers such as S100B and NSE) in Amazonian riverside populations. Three hundred eighty-eight individuals, selected after inclusion and exclusion criteria were studied. The genotype of apolipoprotein E more frequent was ɛ3/ɛ3, followed by ɛ3/ɛ4. Allelic frequencies were 0.043: 0.784: 0.173 to ε2: ɛ3: ɛ4, respectively. The median level of total mercury in hair was 4.2 μg/g (1.9- 10.2). A significant proportion of participants (24.8%) had mercury levels above 10 μg/g, as recommended by the WHO limit, and 12.8% of participants showed a total content of mercury greater or equal to 20 μg/g. Interestingly, Tucuruí levels were much higher than levels in the Tapajós (area recognized by the presence of mining gold activity). We identified 29% of patients with ApoE4 (considered at risk) and 8 maximum risk individuals (carriers of ApoE4 and mercury content above the limit of 10 μg/g). Moreover, there was a significant difference in mRNA levels of S100B protein between groups exposed to high and low levels of mercury. For the first time, markers of the three spheres of influence in human toxicology (exposure, susceptibility and poisoning) were studied. Our data already support the use of these markers to monitoring the Amazonian populations. This knowledge will assist the development of prevention strategies and making government decisions facing the problem of the impact of the mercury in the Amazon.
Acesso aberto (Open Access)
Análise do crescimento e perfil bioacumulativo da cianobactéria Geitlerinema unigranulatum UFV-E01 na presença de arsenato de sódio
(Universidade Federal do Pará, 2012-07-31) GOMES, Laise de Azevedo; SCHNEIDER, Maria Paula Cruz; http://lattes.cnpq.br/3901112943859155
Arsenic is a toxic metalloid that has become a public health problem worldwide. In order to reduce the environmental contamination by this metalloid, which is derived from natural and anthropogenic activities, the use of micro-organisms in bioremediation process has shown to be a promising strategy. A filamentous homocitada cyanobacterium belonging to the order Pseudanabaenales, Geitlerinema unigranulatum UFV-E01, was isolated from an environment contaminated by arsenic, suggesting an ability to deal with the toxic effect of this metalloid. In view of this, this study aimed to characterize the resistance to sodium arsenate and quantify the total arsenic extracellular cyanobacterium G. unigranulatum UFV-E01. Analyses of sodium arsenate resistance showed that the cyanobacterium was able to grow in 50 mM for 20 days. Furthermore, the cyanobacterium G. unigranulatum UFV-E01 accumulated sodium arsenate for 10 days, reducing up to 67% arsenic extracellular. From the data obtained in this study, the cyanobacterium G. unigranulatum UFV-E01 was able to withstand high concentrations of sodium arsenate, although other analysis, the characterization of the metabolic pathways involved in the resistance must be taken to consider their use in environments impacted by arsenic.
Acesso aberto (Open Access)
Análise do efeito tóxico e alterações transcriptomicas de células neuronais e gliais após exposição ao fluoreto
(Universidade Federal do Pará, 2019-05-23) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Corrêa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Despite being widely used in dentistry for dental carie control, in high amounts fluoride may be associated with side effects of which the best known is dental fluorosis. In addition, studies suggest that even at low concentrations fluoride may exerts toxicity leading to damage on CNS. Functional toxicogenomics analysis of gene profile after exposure to contaminants has been used as a tool for the identification of biomarkers of exposure, as well as for the identification of signaling pathways that may be used for treatment and / or prevention of damage caused by the toxicity of certain compounds. As the molecular mechanism of fluoride toxicity still unknow, analysis of F chronic exposure on gene expression profile of CNS cells are necessary. Here we aimed to show the effect of fluoride exposure of plasma concentration founded on population that used to be exposed to fluoridated drink water, on the main CNS cells. In this way, we have used human cell lineage IMR-32 (neurons) and U87 (glial cells) to analyze parameter of viability, morphology and cell metabolism, ATP-synthesis, oxidative stress, DNA damage and global gene expression profile after 10 days exposure. Our results have shown that fluoride does not induce changes in IMR-32 cells. On the other hand, it induces cell death by necrosis, increased metabolism, decrease in ATP and GSH / GSSG in U87 cells and DNA fragmentation. The U87 gene expression profile is differentially altered after fluoride exposure, decreasing 1735 genes and an increasing expression of 1047 genes after exposure to 0.095μg / mL and decreasing of 1863 gene expression and increasing of 1023 expression after exposure to 0.22μg / mL. We also highlighted the major molecular pathways altered after exposure, such as the signaling pathway TNF-alpha via NFK-B and mitochondrial process. We also showed genes with significant importance biology (hub genes) such as the genes PTGES3, EP300, CYP1B1, RPS27A. Our results suggests that glial cell are affected by fluorides exposure and mitochondria has a major role on the mechanism of fluoride toxicity.
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/4362051219348099
The 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.
Acesso aberto (Open Access)
Avaliação bioquímica, hormonal e de parâmetros de crescimento na exposição pós-natal ao metilmercúrio em ratos wistar
(Universidade Federal do Pará, 2016-08-19) XAVIER, Fábio Branches; PINHEIRO, Maria da Conceição Nascimento; http://lattes.cnpq.br/6353829454533268
The effects of methylmercury on growth hormone and its relation to liver function, weight and growth were evaluated in an experimental model of acute and subchronic exposure with mercury. Forty wistar rats were divided into four groups: control, acute, subchronic2 (SB2) and subchronic3 (SB3). Measurements of total mercury (HgT), growth hormone (GH), glucose, ALT and AST enzyme activities, body weight and length of animals were measured in all groups. The results demonstrated that the dose of 25mg/kg was lethal for all animals in this group. The concentrations of mercury measured in the hair’sfrom the SB2 and SB3 groups were significantly higher than in the control group. GH levels were elevated in the acute group and reduced in the subchronic groups. The reduction of glycemia in the subchronic groups was highly significant in relation to the control group (p <0.01). The ALT and AST enzyme activities were altered. These results suggest that methylmercury high doses administered is hepatotoxic, able of to compromise glycemic control and to promote significant alterations in GH levels, which may interfere in the growth of the animals. However, other studies are required to understand the alterations found.
Acesso aberto (Open Access)
Avaliação da sensação posicional de articulações dos membros superiores em sujeitos expostos cronicamente ao metilmercúrio
(Universidade Federal do Pará, 2014-11-29) OLIVEIRA, Alexandre Rodrigo Batista; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718
The Exposure of mercury in some watersheds in the Amazon has chronic character and a mild and moderate intensity. Communities of the basin in the Tapajos River has been monitored about the levels of mercury in the hair over the past 20 years and it was observed that the concentration of mercury in the hair of these people has high levels when compared with other riparian regions, without gold mining activities. In accidents occurred on Minamata in Japan, one of the most common symptoms was the loss of the somestetic function. Proprioception is a somestetic function that can be used to monitor the effects of prolonged exposure to mercury in populations. This work aims to study the sensation of positional joints of upper limb of subjects chronically exposed to mercury and with high levels in the last 3 years and compare the results of this assessment with those obtained in populations with less exposure to methylmercury. Fifty-seven volunteers have agreed to participate in this study, 23 of which belonged to group subjects chronically exposed to mercury from the community of barriers and 34 subjects belonged to the group with lower exposure to mercury from the community of Alter do Chão. Each subject had the positional sensations of joints of the shoulder, elbow and wrist evaluated by 3 times under conditions of open and closed eye. The evaluation consisted of teaching the subject to move a segment of the upper limb (forearm, hand or arm) from a neutral position to a position to articulate target. Each time the subject ended the movement was photographed the final position with digital photo camera of high resolution spatial and temporal. To calculate the articular amplitude at the end of the movement was used the program KINOVEA®, in which allows you to open the photo and use a digital tool to measure the angulation between the proximal and distal segment of the joint in question. Middle articular amplitude values for the open eye condition were statistically higher in the exposed group than in the control group in all the joints, while for the closed eye condition the values exposed group was statistically lower than in the control group only in the wrist joint. There was no statistical difference for the relative difference of angular joint positioning values between the study groups in all joints examined. The exposed group showed lower coefficient of variation for the test condition with the eye open in the joints of the wrist and elbow. The exposed group showed the highest coefficient of variation for the test condition with the eye closed only in the wrist joint. The angular difference values were sequentially higher proximal joints to the distal articulation in the exposed group, however in the control group the angular difference was similar in all the joints. The subjects chronically exposed to mercury showed slight alterations of the joint position sensation when compared with a control group. Proprioceptive evaluation can be an inexpensive tool for the assessment of the effects of mercury on the health of coastal populations exposed to the metal.
Acesso aberto (Open Access)
Avaliação dos efeitos decorrentes da exposição ao cloreto de alumínio sobre parâmetros motores, cognitivos e de estresse oxidativo em ratos
(Universidade Federal do Pará, 2018-12-18) FERNANDES, Rafael Monteiro; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/6791765554367432
Aluminum (Al) is the third most abundant metal in the earth's crust, being present in large amounts in soil and water, its high bioavailability makes it an important environmental contaminant. Al is considered a neurotoxic agent and accumulates in the nervous system, being this behavior associated with several neurodegenerative diseases. However, little is known about its effects at doses similar to human consumption in the nervous and biochemical systems. Thus, this study investigated the effects of chronic exposure to aluminum chloride (AlCl3) on cognition, motor behavior and oxidative stress. For this, adult Wistar rats were divided into three groups: Al1 (8.3 mg / kg / day), Al2 (5.2 mg / kg / day) and Control (Distilled water) being exposed orally for 60 days. After the exposure period, behavioral, histological, oxidative stress parameters and quantification of aluminum levels in the blood were performed. There were no changes in motor behavior, there was change in only one exploratory parameter and in cognition. No differences were found in the population of the purkinje neurons between the experimental groups. Exposure to Al increased levels of this metal in the blood, also altering the parameters of oxidative biochemistry. Thus, we can affirm that exposure to Al in rats, at doses equivalent to urban exposure and in potentially safe doses are capable of promoting breakage of blood homeostasis, altering hippocampal biochemical balance, generating a state of oxidative stress and cognitive damage, not being able to promote significant changes in the cerebellum and motor parameters.
Acesso aberto (Open Access)
Avaliação in vitro dos possíveis efeitos citotóxicos, genotóxicos e mutagênicos das drogas antimaláricas artemisinina e artemeter em linfócitos humanos
(Universidade Federal do Pará, 2012-05-25) CARDOSO, Plínio Cerqueira dos Santos; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Artemisinin is a substance extracted from the Chinese plant Artemisia annua L., and widely used in natural medicine for a treatment of various diseases. Artemether is a substance synthesized from artemisinin. These drugs belong to a special group of molecules called sesquiterpene lactones widely administered in the treatment of malaria. Although considered effective anti-malarial drugs, very little is known about the genotoxic and cytotoxic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin and artemether in cultured human lymphocytes using the comet assay, the micronucleus test and a cytotoxicity assay for detection of necrosis and apoptosis by fluorescent differential acridine orange/ethidium bromide (LA/BE), respectively. Our results showed a significant increase (p<0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p<0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. Thus, it was shown in our work that these two drugs exert mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes under the conditions evaluated. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.
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/3512648574555468
Inorganic 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.
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/4362051219348099
Study 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.
Acesso aberto (Open Access)
Avaliação temporal da exposição humana ao mercúrio no Oeste paraense
(Universidade Federal do Pará, 2015-11-27) ANDRADE, Paulo Douglas de Oliveira; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718
In the present study we described mercury (Hg) exposure evolution in two riverside communities of Tapajos River Basin, Brazilian Amazon. These communities are exposed to this metal by the consumption of fishes that they fishing from the contaminated river. The contamination is due to a process that occurs mainly due to the weathering of soil in the area (which is naturally rich in Hg) and gold mining, that uses mercury to isolate the gold. The analysis used a dosimetric database containing values of mercury, wich was generated from hair samples of the riversides from Tapajos. The data collection was conducted for 17 years (1998-2014) and totaled 1.502 (one thousand, five hundred two) samples, which were divided into four groups: adult male, adult female, male child and female child. The results reveled the group with the highest risk of exposure: the adults males. After all the years of study, the adult male group was the group with the highest average Hg levels (14,41 μg/g ± 10 μg/g). On the other hand, all groups showed a trendy to decrease these levels, with the men took more time to start this process of reduction rates. Their levels dropped from 16,61 μg/g in 2007 to 11,23 μg/g in 2013. Women's group reduced from 13,92 μg/g in 2004 to 7,04 μg/g in 2013. Children had more significant reduction, wherein the girls dropped from 15.42 μg/g in 2001 to 3.83 μg/g in 2014, and the boys from 12.96 μg/g to 5.95 μg/g in the same years. The problematic situation involving the adult male group may indicate a more traditional lifestyle (based on a high fish consumption), less contact with professionals and researchers who instruct the population about the risks of poisoning, and more restrict nutrition, without red meat, tropical fruits, etc. In this sense, it is evident the need for greater awareness of this group in particular (adults males), and must the public health policies aimed specifically, must be enhanced in the region.
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/3512648574555468
Mercury 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.
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/9900144256348265
Cardiovascular 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.
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/3219037174956649
The 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.
Acesso aberto (Open Access)
Estado nutricional e desenvolvimento motor de crianças ribeirinhas expostas ao mercúrio no estado do Pará - Amazônia brasileira
(Universidade Federal do Pará, 2014-11-26) LIMA, Antônio César Matias de; PINHEIRO, Maria da Conceição Nascimento; http://lattes.cnpq.br/6353829454533268
Several studies have shown that riverside children from Amazon are exposed to mercury at levels that can be harm to the development. Although, no previous study evaluated the consequences of exposure to the neurodevelopment of this population. The methods used did not take into account the different interfering factors in the child development. We aim to assess the children's motor development and its relation to mercury exposure, nutritional status and socioeconomic profile of the families of local children in two different geographic regions of Pará, Tapajós river basin (São Luiz do Tapajós and Barreiras communities) and Tocantins river basin (Furo do Maracujá community). The demographic and socioeconomic information of families were obtained through the ABEP socioeconomic questionnaire, 2012. For the analysis of anthropometric measurements the WHO AnthroPlus v 1.0.2 software was used (for children above 5 years). Hair sample were used to quantify the total Hg analysis by atomic absorption spectrophotometry. To analyze the children development was used the Test of Gross Motor Development - Second Edition (TGMD-2) Ulrich (2000). The mercury exposure levels of children in the Tapajos were significantly higher than the children from Tocantins. In all schoolchildren groups the social status were categorized as very poor. Children from São Luiz do Tapajós had higher frequency of underweight and stunting than the other children population. In the overall assessment, Barreiras community showed better performance in manipulative skills, locomotor and gross motor coefficient than the others. There was no difference between the children of São Luiz do Tapajós and Furo do Maracujá that had the worst performers. There was no difference between the children from São Luiz do Tapajós and Furo Maracujá. The correlation between the total Hg and motor development markers was observed in Barreiras, while between body mass index and developing markers were observed in the Furo do Maracujá and Barreiras. These results suggest the influence of mercury on the motor development of school, alone and in association with nutritional factors. The TGMD2 is a viable technique in the evaluation of riparian school engine development and may be recommended for other groups of children with similar socioeconomic conditions for this study.
Acesso aberto (Open Access)
Estresse oxidativo na hepatotoxicidade aos medicamentos anti-tuberculose
(Universidade Federal do Pará, 2016-06-30) COSTA, Maria Heliana Alencar da; MACCHI, Barbarella de Matos; http://lattes.cnpq.br/5330351659478942; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Tuberculosis treatment involves a combination of drugs with possible interactions with each other and other drugs. The most common side effects are related to hepatotoxicity. The biotransformation of drugs may result in the formation of reactive metabolites that can produce cellular damage which has been considered as an important process in the pathogenesis of hepatotoxicity. Goals: Evaluate the role of oxidative stress in patients with hepatotoxicity that have used anti-TB drugs. Methodology: To reach the first goal a Review of hepatotoxicity as an adverse reaction to anti-TB drugs was performed. Such an review was done through a wide search in the Portal of the Virtual Library of Health that targeted Portuguese and English literature to find papers pub- lished until December 2014. On the other hand, a Case Control study was performed to reach the second goal. For the analysis of antioxidant enzymes, patients treated at HUJBB in Secondary Reference Clinic of Pulmonology Clinic and admitted in línica of Pulmonology, and the patients seen at the Basic Health Unit Guamá in Belém were included. Results: As for the literature review, it was found that hepatic impairment is among the highest incidence of adverse reactions associated with anti-tuberculosis drugs in the Brazilian scene and adverse reactions during treatment of tuberculosis are one of the main factors associated with therapy abandonment. Regarding the analysis of antioxidant enzymes, the analysis of glutathione in the control group with hepatotoxicity (PCH) and the group without hepatotoxicity with anti-TB drugs (PCT) achieved median glutathione levels of 221 nmol / ml, 227 nmol / ml, and 236 nmol / ml, respectively. The distribution of catalase in the control group with hepatotoxicity (PCH) and the group without hepatotoxicity with anti-TB drugs (PCT) showed medians of catalase activity with values of 213 nmol / ml, 319 nmol / ml and 2035 nmol / ml, respectively. The median levels of antioxidants glutathione to the PCT group was the largest. However, glutathione levels were not statistically significant when applying the ANOVA test. Distributions of catalase activity in the population of TB patients in the group who developed hepatotoxicity (PCH) and that evolved without hepatotoxicity (PCT) were larger when compared to healthy volunteers. In particular, there was a statistically significant difference in catalase activity in the group (PCT) compared to the remaining groups. Conclusion: The results suggest that hepatotoxicity is not only associated with antioxidants enzymes and further analysis with more explanatory variables should be made to better understand this phenomenon.