Lívia G. Castilhos

Free and nanoencapsulated curcumin prevents cigarette smoke-induced cognitive impairment and redox imbalance.

Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormalities. Curcumin, a natural polyphenol, have shown to be able to prevent cigarette smoke-induced cognitive impairment. Here, we investigated possible mechanisms involved in curcumin protection against cigarette smoke-induced cognitive impairment and, due to its poor bioavailability, we investigated the potential of using curcumin-loaded lipid-core nanocapsules (C-LNC) suspension. Rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. Animals were divided into ten groups: I, control (vehicle/corn oil); II, curcumin 12.5mg/kg; III, curcumin 25mg/kg; IV, curcumin 50mg/kg; V, C-LNC 4 mg/kg; VI, tobacco exposed; VII, curcumin 12.5mg/kg along with tobacco exposure; VIII, curcumin 25mg/kg along with tobacco exposure; IX, curcumin 50mg/kg along with tobacco exposure; X, C-LNC 4 mg/kg along with tobacco exposure. Cigarette smoke-exposure impaired object recognition memory (P<0.001), indicated by the low recognition index, increased biomarkers of oxidative/nitrosative stress such as TBARS (P<0.05) and NOx (P<0.01), decreased antioxidant defenses such as NPSH content (P<0.01) and SOD activity (P<0.01) and inhibited the activities of enzymes involved in ion homeostasis such as Na(+),K(+)-ATPase and Ca(2+)-ATPase. Both curcumin formulations (free and nanoencapsulated) prevented the memory impairment, the redox imbalance and the alterations observed in the ATPases activities. Maintenance of ion homeostasis and redox balance is involved in the protective mechanism of curcumin against tobacco-induced cognitive impairment. Our results suggest that curcumin is a potential therapeutic agent for neurocognition and that C-LNC may be an alternative to its poor bioavailability.

Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in poloxamer 407 induced hyperlipidemia in rat brain.

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

Effect of Uncaria tomentosa extract on purinergic enzyme activities in lymphocytes of rats submitted to experimental adjuvant arthritis model.

BackgroundConsidering that adjuvant arthritis is an experimental model of arthritis widely used for preclinical testing of numerous anti-arthritic agents, which were taken by a large number of patients worldwide, it is of great interest to investigate the therapeutic action of compounds with anti-inflammatory properties, such as Uncaria tomentosa extract. Moreover, there are no studies demonstrating the effect of U. tomentosa on the metabolism of adenine nucleotides published so far. Thus, the purpose of the present study is to investigate the effects of U. tomentosa extract on E-NTPDase and E-ADA activities in lymphocytes of Complete Freund’s Adjuvant (CFA) arthritis induced rats.MethodsTo evaluate the effect of U. tomentosa extract on the activity of E-NTPDase and ADA in lymphocytes, the rats were submitted to an experimental adjuvant arthritis model. Peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Data were analyzed by a one- or two-way ANOVA. Post hoc analyses were carried out by the Student-Newman-Keuls (SNK) Multiple Comparison Test.ResultsE-NTPDase activity was increased in arthritic untreated. Arthritic rats which received U. tomentosa extract, presented similar results to the control group. However, results obtained for adenosine hydrolysis by E-ADA were not altered in arthritic rats. U. tomentosa extract did not alter E-NTPDase and E-ADA activity in healthy animals.ConclusionsThe present investigation supports the hypothesis that the increased E-NTPDase activity verified in arthritic rats might be an attempt to maintain basal levels of ATP and ADP in the extracellular medium, since the arthritis induction causes tissue damage and, consequently, large amounts of ATP are released into this milieu. Also, it highlights the possibility to use U. tomentosa extract as an adjuvant to treat arthritis.

Efeitos in vitro de ocratoxina A, deoxinivalenol e zearalenona sobre a viabilidade celular e atividade de E-ADA em linfócitos de frangos de corte¹

Micotoxinas representam um vasto grupo de contaminantes quimicos naturais originados a partir do metabolismo secundario de fungos filamentosos patogenicos. Elas sao produzidas, principalmente, pelos generos Fusarium, Alternaria, Aspergillus e Penicillium, os quais podem contaminar graos e cereais, como trigo, milho e soja. Conforme sua natureza e niveis de concentracao, micotoxinas podem induzir efeitos toxicos em animais de producao e humanos. Um estudo in vitro foi realizado para avaliar a susceptibilidade das celulas linfocitarias de frangos de corte a diferentes concentracoes de ocratoxina A, deoxinivalenol e zearalenona. Cada micotoxina foi adicionada ao meio celular em diferentes concentracoes (0,001; 0,01; 0,1 e 1μg/mL). A viabilidade celular e atividade de ecto-adenosina desaminase foram analisadas em 24, 48 e 72 horas atraves de ensaios colorimetricos. Para isso, foram utilizados 0,7x105 linfocitos/mL em meio RPMI 1640, suplementado com 10% de soro fetal bovino e 2,5 UI de penicilina/estreptomicina por mL, incubados em atmosfera de 5% de CO2 a 37 °C. Todos os experimentos foram realizados em triplicata e os resultados foram expressos como media e erro padrao da media. Os resultados obtidos demonstraram que tanto ocratoxina A como deoxinivalenol induziram proliferacao linfocitaria e baixa atividade enzimatica in vitro (P 0,05). Foi possivel correlacionar os dados referentes a viabilidade celular e atividade de ecto-adenosina desaminase, sugerindo que, em concentracoes minimas, as micotoxinas testadas nao estimularam a atividade da enzima, que possui acao pro-inflamatoria e contribui para o processo de imunossupressao e, portanto, evitando um decrescimo na viabilidade celular. Este e o primeiro estudo feito com OCRA, DON e ZEA sobre linfocitos de frangos de corte em cultivos in vitro na avaliacao desses parâmetros.

Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats

Hyperlipidemia is a group of disorders characterized by excessive lipids in the bloodstream. It is associated with the incidence of cardiovascular diseases and recognized as the most important factor underlying the occurrence of atherosclerosis. This study was conducted to investigate whether pretreatment with quercetin can protect against possible memory impairment and deterioration of the cholinergic system in hyperlipidemic rats. Animals were divided into ten groups (n=7): saline/control, saline/quercetin 5mg/kg, saline/quercetin 25mg/kg, saline/quercetin 50mg/kg, saline/simvastatin (0.04mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5mg/kg, hyperlipidemia/quercetin 25mg/kg, hyperlipidemia/quercetin 50mg/kg and hyperlipidemia/simvastatin. The animals were pretreated with quercetin by oral gavage for a period of 30days and hyperlipidemia was subsequently induced by intraperitoneal administration of a single dose of 500mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. The results demonstrated that hyperlipidemic rats had memory impairment compared with the saline control group (P<0.001). However, pretreatment with quercetin and simvastatin treatment attenuated the damage caused by hyperlipidemia compared with the hyperlipidemic group (P<0.05). Acetylcholinesterase (AChE) activity in the cerebral hippocampus was significantly (P<0.001) reduced in the hyperlipidemic group compared with the control saline group. Pretreatment with quercetin and simvastatin treatment in the hyperlipidemic groups significantly (P<0.05) increased AChE activity compared with the hyperlipidemic group. Our results thus suggest that quercetin may prevent memory impairment, alter lipid metabolism, and modulate AChE activity in an experimental model of hyperlipidemia.

Influence of Toxoplasma gondii Acute Infection on Cholinesterase Activities of Wistar Rats

Several studies have shown the mechanisms and importance of immune responses against Toxoplasma gondii infection and the notable role of cholinesterases in inflammatory reactions. However, the association between those factors has not yet been investigated. Therefore, the aim of this study was to evaluate the acetylcholinesterase (AChE) activity in blood and lymphocytes and the activity of butyrylcholinesterase (BChE) in serum of rats experimentally infected with T. gondii during the acute phase of infection. For that, an in vivo study was performed with evaluations of AChE and BChE activities on days 5 and 10 post-infection (PI). The activity of AChE in blood was increased on day 5 PI, while in lymphocytes its activity was enhanced on days 5 and 10 PI (P<0.05). No significant difference was observed between groups regarding to the activity of BChE in serum. A positive (P<0.01) correlation was observed between AChE activity and number of lymphocytes. The role of AChE as an inflammatory marker is well known in different pathologies; thus, our results lead to the hypothesis that AChE has an important role in modulation of early immune responses against T. gondii infection.

Increased oxidative stress alters nucleosides metabolite levels in sickle cell anemia

ABSTRACT Objectives: This study was conducted to assess the markers of oxidative stress, myeloperoxidase (MPO), acetylcholinesterase (AChE) and xanthine oxidase (XO) activities as well as the levels of nucleotide metabolites in sickle cell anemia (SCA) patients. Methods: Fifteen SCA treated patients and 30 health subjects (control group) were selected. The markers of oxidative stress (levels of reactive oxygen species (ROS), plasma proteins, carbonyl content, lipid peroxidation (TBARS), total thiols (T-SH), glutathione and catalase activity), MPO, AChE and XO activities as well as the levels of nucleotide metabolites were measured in SCA patients. Results: ROS, thiobarbituric acid-reactive substances (TBARS) and T-SH levels as well as the activities of catalase and MPO were significantly increased while glutathione level was reduced in SCA patients. Furthermore, a significant (P < 0.001) increase in hypoxanthine level was demonstrated in SCA patients. However, the serum levels for xanthine (P < 0.01) and uric acid (P < 0.001) were decreased in SCA patients. A significant (P < 0.001) decrease in XO activity was detected in SCA patients. Discussion: The altered parameters in SCA patients suggest that the generation and impairment of oxidative stress in this disease as well as antioxidant markers are contributory factors towards cellular redox homeostasis and alteration of purine metabolites.

Hesperidin attenuates inflammation and oxidative damage in pleural exudates and liver of rat model of pleurisy

ABSTRACT Objectives: This study investigated the potential anti-inflammatory effect of hesperidin against carrageenan induced pleurisy in rat model. Methods: Twenty-four adult female Wistar rats (350 - 450g) were grouped as follows: Group I: rats were administered saline solution only (Normal control group); Group II: rats were administered saline solution (NaCl 0.9%) orally and injected with carrageenan (Inflammation control group); Group III: rats were administered hesperidin only (Hesperidin group); Group IV: rats were administered hesperidin orally and intrapleurally injected with 2% carrageenan (Inflammation treated with hesperidin group). The exudate volume, total leukocyte count, reactive oxygen species (ROS), myeloperoxidase (MPO),δ–aminolevulinate dehydratase (δ-ALA-D), catalase (CAT), superoxide dismutase (SOD), activities as well as non-protein thiol group (NPSH) and thiobarbituric acid reactive substances (TBARS) levels were determined. Results: Pretreatment with hesperidin at a dose of 80 mg/kg orally per day for 21 days, minimized the increase in pleural exudate volume and leucocyte count and modulated the activities of MPO, SOD and CAT, as well as the levels of ROS, NPSH and TBARS in carrageenan-induced rats. Conclusion: Our results suggest that hesperidin can elicit its anti-inflammatory action by blocking exudate and leukocyte influx into pleural cavity, inhibiting MPO activity and preventing oxidative damage.

POLÍTICAS PÚBLICAS E A ATUAÇÃO DOS GESTORES FRENTE AO CÂNCER DE MAMA E DO COLO UTERINO

Objetivo: descrever sobre as politicas publicas nas neoplasias de mama e do colo uterino, assim como a atuacao dos gestores nestes cânceres. Metodologia: revisao narrativa da literatura, realizada nas bases de dados: scielo, pubmed e lilacs. Resultados: selecionou-se 42 artigos, datados de 1984 a 2014. os descritores utilizados foram: neoplasia de mama, neoplasia do colo do utero, politicas publicas e gestor de saude. foi possivel observar que as producoes cientificas buscam orientar a populacao sobre a promocao, a prevencao e o tratamento do câncer de mama e do colo uterino, atraves de politicas publicas. mostram tambem as responsabilidades dos gestores do sus na conducao das acoes nesta area. Consideracoes Finais: para que sejam efetivas estas politicas e preciso garantir que os gestores sejam parceiros no planejamento e na execucao das mesmas, contribuindo para a prevencao do câncer, melhorando a qualidade de vida e prevencao de outras patologias. Descritores: Neoplasia de Mama; Neoplasia do Colo do Utero; Politicas Publicas; Gestor em Saude.

ATENÇÃO PRIMÁRIA E DOENÇA FALCIFORME: UMA REVISÃO SOBRE O PAPEL DO GESTOR

O objetivo deste estudo foi realizar na literatura uma revisao sistematica de artigos cientificos que mencionem a respeito do papel do gestor na atencao primaria a saude e na garantia da adesao ao tratamento dos pacientes portadores de anemia falciforme. Foi realizada busca em diferentes bases eletronicas de dados (Literatura Latino-Americana e do Caribe em Ciencias da Saude, Medical Literature Analysis and Retrieval System Online, US National Library of Medicine National Institutes of Health, e no Scientific Electronic Library Online) no periodo de maio de 2004 a maio de 2014, utilizando os seguintes descritores: gestao em saude, atencao primaria a saude, anemia falciforme e terapeutica. Os usuarios do sistema reportam um atendimento inadequado por parte dos profissionais da saude devido a desinformacao sobre a doenca, assim como a falta de acesso aos medicamentos essenciais nas unidades basicas de saude. Uma maior enfase por parte dos gestores sobre a doenca falciforme deve ser dada na educacao dos profissionais de saude atuantes nas unidades basicas. Embora posteriormente o usuario necessite de ambulatorios de atencao secundaria, tudo deve estar atrelado a atencao primaria, a qual deve coordenar o fluxo e acompanhar o usuario. Descritores: Gestao em Saude; Atencao Primaria a Saude; Anemia Falciforme; Terapeutica.