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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior In this research we observed the effects of different anabolic androgenic steroid administration for protocols (EAA), selecting two molecules, Boldenone (BOL) and Stanozolol (ST).Among the used protocols, Protocol I, represents users who want to accelerate the anabolic effects using higher than recommended doses, in a shorter period of time, the Protocol II represents groups of anabolic steroid users, who elect a moderate dose and time intermediate and protocol III, which represents users that reduce the dose and prolong the exposure time for the purpose of decreasing androgenic effects. Our findings strongly suggest that the treatment with BOL and ST affect the anxiety, dominance and aggression behavior in mice dose and time of exposuredependent. Furthermore, it is emphasized that the memory impairment induced by boldenone is correlated with the increase of acetyl cholinesterase (AChE) activity in cerebral cortex and hippocampussuggesting that a dysfunction of the cholinergic system may be involved in the mechanism of this alteration, along with the damage associated with oxidative stress as well described in our results. Simultaneously, we evaluated the impact of these treatments on the morphology and oxidative stress parameters in the testes of rats. The increased of oxidative and nitrosative stress markers was evident, as well as significant changes in the normal morphology of the testicle, which is probably associated with the presence of these reactive species.The mechanisms by which the EAA interfere with testicular physiology and behavioral changes have not been deeply studied by our group, but there is strong evidence of the involvement of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in development. Our data shows that EAA, even at low doses, might result in a neuropathological consequences. Similarly, in the testis, no protocol proved to be safe in removing the possibility of reproductive disturbances that could lead to long-term sterility. Na presente tese verificamos os efeitos de diferentes protocolos de adiministração de esteróides androgênicos anabolizantes (EAA) utilizando duas diferentes moléculas frequentemente eleitas pelos usuários, a Boldenona (BOL) e o Estanazolol (ES). Dentre os protocolos utilizados, o protocolo I, representa os usuários que desejam acelerar os efeitos anabólicos usando doses superiores às recomendadas, em um intervalo de tempo mais curto, o protocolo II representa grupos de usuários de esteróides anabolizantes, que elegem uma dose moderada e tempo intermediário e protocolo III, que representa usuários que reduzem a dose e prolongam o tempo de exposição com o objetivo de diminuir os efeitos androgênicos.Nossos dados sugerem fortemente que o tratamento com BOL e ES afetam o comportamento de ansiedade, dominância e agressividade em ratos de forma dependente da dose e do tempo de exposição. Além disso, destaca-se que a perda da memória induzida pela BOL correlaciona-se com o aumento da atividade da acetilcolinesterase (AChE) no córtex cerebral e no hipocampo, e que essa disfunção do sistema colinérgico poderia estar envolvido no mecanismo dessa alteração, somado ainda ao dano associado ao estresse oxidativo também descrito em nossos resultados. Ao mesmo tempo, avaliou-se o impacto desses tratamentos sobre a morfologia e os parâmetros de estresse oxidativo dos testiculos de ratos. Foi evidenciado a elevação dos marcadores de estresse oxidativo e nitrosativo assim como alterações significativas na morfologia normal do testiculo, que provavelmente está associado a presença dessas espécies reativas. Ainda que não tenhamos aprofundados os mecanismos pelos quais os EAA interferem com a fisiologia testicular e as alterações comportamentais, está claro que há um envolvimento das espécies reativas de oxigênio (ERO) e espécies reativas de nitrogênio (ERN) no desenvolvimento das mesmas. Nossos dados levantam a preocupação de que os EAA, mesmo em pequenas doses, possam provocar consequências neuropatológicas levando a alterações comportamentais distintas de acordo com o protocolo utilizado. Da mesma forma, no testiculo, não houve protocolo seguro que descartasse a possibilidade de alterações reprodutivas que poderiam a longo prazo levar a esterilidade.

Conselho Nacional de Desenvolvimento Científico e Tecnológico Anabolic androgenic steroids (AAS) are synthetic substances derived from testosterone that promote greater muscle mass and strenght. Thus, they are used illegally to improve athletic performance of horses, dogs or athletes or to improve meat production. The doses, ranging from 10 to100 times the therapeutic recommendation, enhances the deleterious effects on various organs. The objective of this study was to evaluate the effects of different protocols (P1, P2 and P3) of boldenone undecylenate (BU) and stanozolol (ST) on markers of liver and kidney function and variables of oxidative stress in these organs. For this, 54 male Wistar rats were divided into nine groups of six animals each. Each animal received intramuscularly 5.0 mg kg-1 of BU or ST once a week for four weeks (P1); 2.5 mg kg-1 of BU or ST once a week for eight weeks (P2); and 1.25 mg kg-1 of BU or ST once a week for 12 weeks (P3). For each protocol, a control group was used (CG), and they received 0.1 ml of olive oil intramuscularly. Blood, and fragments of liver and kidney were collected for alanine aminotransferase activity (ALT), alkaline phosphatase (ALP), albumin, creatinine, cholesterol, total protein, triglycerides, urea, reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), total thiols (T-SH), and glutathione (GSH) evaluation. Seric ALT activity and cholesterol concentration were significantly (p0,05) da ALT em relação ao grupo controle no protocolo P2. No tecido hepático, comparando-se os grupos UB e GC, obteve-se níveis maiores (p

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Sporotrichosis is an implantation mycose, caused by species complex Sporothrix spp., considered the subcutaneous mycosis with higher occurrence and importance in the Americas, this thermally dimorphic fungus induces a chronic inflammatory granulomatous response in their hosts. The cholinesterase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are the "key" enzimes signal in inflammatory and immune processes, for regulating the levels of ACh, the main neurotransmitter "cholinergic antiinflammatory pathway". The cholinesterase activity has been demonstrated in various inflammatory conditions; however, there is no evidence of his participation in sporotrichosis. The objective of this study was to report a case of feline sporotrichosis by natural infection; evaluate the activities of AChE in the lymphocytes and whole blood; evaluate the activity of BChE; cytokines (IL1, IL6, TNF, and IL-10 INFγ) and immunoglobulins (IgA, IgG, IgM, IgE) in serum of rats experimentally infected with S. schenckii. Sixty-three rats were divided into three groups, control group (CG), group by subcutaneous infection (GSC) and group by intraperitoneal infection (GIP). Blood collection for activities evaluation of cholinesterase, cytokines and immunoglobulins were held on 15, 30 and 40 post-infection (PI). The GIP, had an increase in the activity of AChE in the blood in all experimental times, the increase in lymphocytes occurred only on 30 and 40 days PI. The increase of the enzyme suggests a decrease in the levels of ACh with consequently increased IL-1, IL-6, TNF-α, INF-γ, as observed in this study. In the acute phase of infection wants an intense inflammatory response in an attempt to remove the agent. However, with the chronicity of infection if the stimulus is maintained can lead to remarkable tissue injury. Regarding the chronic process observed in GIP, 30 and 40 days PI, that IL-10 was shown to be increased, but not enough to contain inflammation, as pro cytokines, continued high levels. Conversely, what happened in the GIP, the SC group had reduced levels of IL-10 at all times PI, this decrease can lead to tissue damage by not blocking the inflammatory response. The activity of AChE in the GSC only statistically increased in lymphocytes, at 40 days PI. There was no significant activity when assessing the BChE, in both groups, except in the GSC 40 days PI. The BChE is not efficient in Ach s hydrolysis in low concentrations, but it can replace the AChE when itself is inhibited. High levels of immunoglobulins in all groups and at all times, shows the induction of humoral immune response in sporotrichosis. Thus, the increase in the AChE activity in whole blood and lymphocytes, together with high levels of serum immunoglobulins and cytokines, suggesting the involvement of cholinesterases, and in immune cell response against infection by S. schenckii. A esporotricose é uma micose de implantação, causada pelo complexo de espécies Sporothrix spp., considerada a micose subcutânea com a maior ocorrência e importância nas Américas, esse fungo termodimórfico induz uma resposta inflamatória granulomatosa crônica em seus hospedeiros. As colinesterases, acetilcolinesterase (AChE) e butirilcolinesterase (BChE) desempenham um papel chave na sinalização de processos inflamatórios e imunes, por regular os níveis de ACh, o principal neurotransmissor da via colinérgica antiinflamatória . A atividade das colinesterases tem sido demonstrada em várias condições inflamatórias, contudo, não há evidencias de sua participação na esporotricose. O objetivo deste estudo foi relatar um caso de esporotricose felina por infecção natural; avaliar as atividades da AChE em linfócitos e no sangue total; avaliar a atividade da BChE; citocinas (IL1, IL6, TNFα, INFγ e IL10) e imunoglobulinas (IgA, IgG, IgM, IgE) no soro de ratos infectados experimentalmente por S. schenckii. Foram utilizados sessenta e três ratos distribuídos em três grupos, grupo controle (GC), grupo por infecção subcutânea (GSC) e grupo por infecção intraperitoneal (GIP). A coleta de sangue para avaliação das atividades das colinesterases, citocinas e imunoglobulinas foram realizadas nos dias 15, 30 e 40 pós-infecção (PI). No GIP, ocorreu um aumento na atividade das AChE no sangue em todos os tempos experimentais, nos linfócitos o aumento ocorreu apenas nos dias 30 e 40 dias PI. O aumento dessa enzima sugere uma diminuição nos níveis de ACh, com consequentemente aumento das IL-1, IL-6, TNFα, INFγ, como observado neste estudo. Na fase aguda da infecção deseja-se uma resposta inflamatória intensa na tentativa de eliminar o agente. Porém, com a cronicidade da infecção, se o estímulo for mantido pode acarretar marcante lesão tecidual. Com relação ao processo crônico observou no GIP, aos 30 e 40 dias PI, que a IL-10 mostrou-se aumentada, porém não sendo suficiente para conter a inflamação, pois as citocinas pró, continuaram com altos níveis. Inversamente o que aconteceu no GIP, o grupo SC obteve níveis reduzidos de IL 10 em todos s tempos PI, este decréscimo pode levar a danos teciduais pelo não bloqueio da resposta inflamatória. A atividade da AChE, no GSC só se mostrou estatisticamente aumentada nos linfócitos, aos 40 dias PI. Não houve atividade estatística significativa ao avaliar a BChE, em ambos os grupos, exceto no GSC 40 dias PI. A BChE não é eficiente em hidrolisar ACh em baixas concentrações, mas ela pode substituir a AChE na hidrolise da ACh quando a mesma estiver inibida. Os altos níveis evidenciados das imunoglobulinas em ambos os grupos e em todo os tempos, demonstra a indução da resposta imune humoral na esporotricose. Assim, o aumento na atividade da AChE em sangue total e em linfócitos, juntamente com os elevados níveis de citocinas e imunoglobulinas séricas, sugere-se o envolvimento dessa colinesterase, na resposta imune e celular frente a infecção por S. schenckii.

Babesiosis and anaplasmosis are part of the complex called Bovine Parasitic Sadness (TPB), a disease that causes high morbidity and mortality in susceptible cattle. It is caused by infection of Babesia bovis and Babesia bigemina protozoa and by the bacterium Anaplasma marginale. The objective of this study was to evaluate oxidative stress parameters in cattle experimentally infected with B. bovis and B. bigemina and the activities of cholinesterase in asymptomatic B. bigemina well as interference of splenectomy in the oxidative balance of cattle infected with A. marginale. For this, three experiments were performed, using 24 young cattle divided into three groups, each consisting of eight animals which: in the first experiment, four control and four infected with attenuated strain of B. bovis, which were observed decrease in erythrocytes count and activities of catalase (CAT) and superoxide dismutase (SOD) in addition to increased levels of thiobarbituric acid reactive substances (TBARS). In Experiment II, we used four cattle control and four infected with attenuated strain of B. bigemina, observed decrease in the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and CAT, and increased levels of TBARS and SOD in infected cattle. And, in Experiment III, four splenectomized cattle and four intact, both groups infected with A. marginale, with no difference between groups in the hematological and enzymatic profile, only observed drop in hematocrit, red blood cell count and hemoglobin concentration, and increased total leukocyte count due to lymphocytosis in both groups. Positive correlations were found between TBARS versus bacteremia and negative between NPSH versus bacteremia in both groups, but the correlations were higher in splenectomized group. From the results it can be inferred that infection with B. bovis causes oxidative balance, in the same way B. bigemina infection induces an oxidative stress condition and changes the atividase cholinesterase even in asymptomatic animals and bacteremia by A. marginale influences lipid peroxidation in independent splenectomy cattle. This study may suggest that oxidative stress and low-grade inflammation markers can be used as auxiliary tool in the early diagnosis of this disease as well as the basis for studies on the use of antioxidants in the diet of cattle to prevent infection and / or reduce the severity of injuries caused by these parasites. A Tristeza Parasitária Bovina (TPB) é uma doença que causa alta morbidade e mortalidade em bovinos suscetíveis, causada pela infecção dos protozoários Babesia bovis e Babesia bigemina e pela bactéria Anaplasma marginale. O objetivo deste estudo foi avaliar parâmetros de estresse oxidativo em bovinos experimentalmente infectados com B. bovis e B. bigemina e as atividades das colinesterases na infecção assintomática por B. bigemina assim como a interferência da esplenectomia no equilíbrio oxidativo de bovinos infectados com A. marginale. Para tanto, foram realizados três experimentos, sendo utilizados 24 bovinos jovens divididos em três grupos experimentais, cada um composto por oito animais sendo: no Experimento I, quatro controles e quatro infectados com cepa atenuada de B. bovis, onde foram observados decréscimo na contagem de hemácias e nas atividades das enzimas catalase (CAT) e superóxido dismutase (SOD) concomitantes com aumento nos níveis das substâncias reativas ao ácido tiobarbitúrico (TBARS). No experimento II, foram usados quatro bovinos controles e quatro infectados com cepa atenuada de B. bigemina, sendo observados decréscimo nas atividades das enzimas acetilcolinesterase (AChE), butirilcolinesterase (BChE) e CAT e aumento nos níveis de TBARS e SOD nos bovinos infectados. E, no Experimento III, quatro bovinos esplenectomizados e quatro intactos, ambos os grupos infectados com A. marginale, não havendo diferença entre os grupos no perfil hematológico e enzimático, apenas observada queda no hematócrito, contagem de hemácias e concentração de hemoglobina e aumento na contagem total de leucócitos devido a um aumento na contagem de linfócitos em ambos os grupos. Foram evidenciadas correlações positiva entre TBARS e a bacteremia e negativa entre NPSH e a bacteremia em ambos os grupos, porém as correlações foram maiores no grupo esplenectomizado. A partir dos resultados pode-se inferir que a infecção por B. bovis causa desequilíbrio oxidativo, da mesma forma que a infecção por B. bigemina induz a uma condição de estresse oxidativo e altera a atividade das colinesterases mesmo em animais assintomáticos e que a bacteremia por A. marginale influencia na peroxidação lipídica em bovinos independente da esplenectomia. Com este estudo, pode-se sugerir que marcadores de estresse oxidativo e de inflamação de baixo grau podem ser utilizados como ferramenta no auxílio do diagnóstico precoce desta enfermidade assim como servir de base para estudos referentes ao uso de antioxidantes na alimentação de bovinos para prevenir a infecção e/ou reduzir a gravidade das lesões causadas por estes parasitas.

Trypanosoma evansi is a protozoan parasite which infects a wide variety of mammalian hosts leading to the development of trypanosomiasis. Several papers have investigated the enzymatic changes in lymphocytes, important cells involved in immune responses, which are important for understanding the pathological mechanism of trypanosomiasis in animals. Among them we highlight the ectoATPases, enzymes that hydrolyze extracellular nucleotides and nucleosides of adenine. The curcumin (cur) has been associated with several beneficial effects associated with its use in animals experimentally infected with T. evansi, since this compound exhibits its properties among inflammatory and anti-parasitic effects. This study aimed to evaluate the activity of enzymes of the purinergic system in lymphocytes of rats supplemented or not with curcumin 30 days before infection with Trypanosoma evansi. Thirty-two adult male Wistar rats were divided into four groups. The uninfected control group (C) received saline intraperitoneally (IP), the infected control group (CI) received by the same route 0.2 ml of blood with 1x106 parasites and treatment with corn oil. The group pre-infection 20 (PreI20) received 20mg/kg curcumin and pre-infection group 60 (PreI60) received 60mg/kg of curcumin for 30 days prior to inoculation with T. evansi. After inoculation, the 03 treated groups continued to receive daily curcumin within 15 days before euthanasia. The NTPDase activity for both the hydrolysis of ATP to ADP increased significantly in the infected control group compared to the control group (P

Conselho Nacional de Desenvolvimento Científico e Tecnológico Rangelia vitalii is the etiologic agent of rangeliosis, a hemorrhagic disease that was described in dogs from South and Southeast Brazil, Uruguay and Argentina. The immunological aspects involved in this disease have not been fully elucidated. This study aimed to investigate the immunological parameters in rangeliosis by the determination of serum cytokines, nitric oxide, electrophoretic profile, acute phase proteins and immunoglobulins of dogs experimentally infected with R. vitalii. Twelve dogs were divided into two groups: Group A (control) composed by uninfected animals (n=5) and Group B consisting of animals inoculated with R. vitalii (n=7). After inoculation, animals were monitored by blood smear. Blood samples were collected through the jugular vein on days 0, 10 and 20 post-inoculation (PI) to determine the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), oxidation products of nitric oxide (NOx), electrophoretic profile, acute phase proteins (C-reactive protein and alpha 1 acid glycoprotein) and immunoglobulins (IgG, IgM, IgA and IgE). The parasite was found within erythrocytes, neutrophils and monocytes on day 5 PI in infected group. This study showed an increase (P

Conselho Nacional de Desenvolvimento Científico e Tecnológico The pathogenesis of Trypanosoma evansi (T. evansi) infection on central and peripheral nervous system (CNS) and immunologic system it is not completely understood. This study was conducted to investigate the effects of infection by T. evansi on the behavioral performance of rats, relating them to neurochemical alterations of the glutamatergic system and activity of important enzymes such as Ca2 + ATPase, Na + / K + ATPase and acetylcholinesterase (AChE) in the brain. Furthermore, we evaluated the activity of AChE in the T. evansi, using a biochemical protocol and discussed some possibilities for the interaction between the presence of this enzyme in the parasite and its possible relation with the host. Also, we investigated the in vivo effect of curcumin as an antitrypanosomal agent to contribute in the search for new therapies. To this end, we conducted a series of studies, as follow that are presented as scientific articles: in the Article I are presented data from rats experimentally infected with T. evansi and in which the activity of AChE in total brain, cerebellum and blood and plasma butyrylcholinesterase activity on days 3 (T3) and 5 (T5) post infection (pi) were evaluated. In the Article II trypanosomes were isolated by Dietil Amino Etil-celulose column to perform enzymatic assays of AChE activity in the parasite. Article III presents the results of daily oral administration of Curcumin (20 or 60 mg / kg) as a preventive treatment (for 30 or 15 days pre-infection) or as curative treatment (for 15 days pi) for T. evansi infection in rats. The animals were evaluated for parasitemia, proinflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6) and anti-inflammatory (IL-10) in plasma. Also blood AChE activity was studied. In the manuscript I were evaluated behavioral changes (memory and anxiety), glutamate uptake, activity of AChE and ATPases (Ca +2 and Na +, K +) in brain structures of T. evansi infected rats (5 and 30 dpi). Together these studies suggest that rats infected with T. evansi have cognitive impairment, probably caused by changes on energy metabolism (ATPases) and in the cholinergic and glutamatergic systems. That way, alterations observed during behavioral tests probably indicate the progression of clinical disease as a result of neurochemical dysfunction. It was also demonstrated that it is possible to biochemically detect the AChE activity in the T. evansi and this could cause the hydrolysis of acetylcholine in the parasite. It was also demonstrated that pretreatment with curcumin induces immunomodulatory effects, altering inflammatory cytokines and activity of AChE in rats infected with T. evansi. The treatments reduced parasitic load and mortality. Therefore, curcumin should be considered as a feeding supplement in trypanosomiasis endemic areas. Com este trabalho, buscou-se compreender os mecanismos da patogenia do Trypanosoma evansi no sistema nervoso central (SNC), periférico e imunológico. Para isso, foram avaliados os efeitos da infecção por T. evansi sobre o desempenho comportamental de ratos, relacionando-os com alterações neuroquímicas do sistema glutamatérgico e com as atividades de importantes enzimas cerebrais como a Ca+2ATPase, a Na+/K+ATPase e a acetilcolinesterase (AChE). Avaliou-se também, a atividade da AChE no T. evansi usando um protocolo de bioquímica, buscando discutir algumas possibilidades de interação entre a presença desta enzima no parasita e suas possíveis relações com o hospedeiro. Também, foi investigado o efeito in vivo da curcumina como agente tripanocida, a fim de contribuir na busca de novas terapias. Com estes propósitos, foram realizadas varios estudos, sendo: no artigo I buscou-se avaliar se a infecção pelo protozoário altera o sistema colinérgico. Para isso, foram utilizados ratos experimentalmente infectados com T. evansi e avaliada a atividade da AChE no cérebro total, no cerebelo e no sangue e a atividade da butirilcolinesterase plasmática nos dias 3 e 5 pós infecção (pi); no artigo II tripanossomas foram isolados por coluna de dietilaminoetilcelulose para realizar ensaios enzimáticos da atividade da AChE no parasito; no artigo III doses diárias de Curcumina (20 ou 60 mg / kg) diluída em óleo de milho foram administradas diariamente por via oral (gavagem) como tratamento preventivo (30 ou 15 dias pré-infecção) e como tratamento durante quinze dias pi. Os animais foram avaliados quanto a parasitemia, as citocinas pró-inflamatórias (IFN-γ, TNF-α, IL-1, IL-6) e anti-inflamatória (IL-10) plasmáticas e a atividade sanguínea da AChE; no manuscrito I foram avaliadas as alterações comportamentais (memória e ansiedade), a captação de glutamato, atividade da AChE e das ATPases (Ca +2 e Na +, K +) nas estruturas encefálicas nos dias 5 e 30 de ratos infectados com T. evansi. Com estes estudos, pode-se concluir que ratos infectados com T. evansi apresentam déficit cognitivo, provavelmente causados por alterações nos parâmetros do metabolismo energético (ATPases) e nos sistemas colinérgico e glutamatérgico, sugerindo que as alterações observadas durante testes comportamentais provavelmente indicam uma disfunção neuroquímica. Também foi demonstrado que é possível detectar bioquimicamente a atividade da AChE no T. evansi e esta deve ser responsável pela hidrólise da acetilcolina no parasita. Quando os animais infectados foram tratados com curcumina demonstrou-se que o pré-tratamento com este composto induz efeitos imunomodulatórios, alterando os parâmetros inflamatórios tais como as citocinas e a atividade da AChE sanguínea. Desta forma, sugere-se que a curcumina pode ser utilizada como um suplemento alimentar em áreas endêmicas de tripanossomíase, uma vez que reduziu a carga parasitária e a mortalidade em ratos infectados com T. evansi, contribuindo assim com novas alternativas de tratamento.

Diabetes mellitus (DM) is an important health problem that affects worldwide human population and is commonly observed in small animal clinics. Many studies show that hyperglycemia is the pivotal cause of DM complications, including cataract, nephropathy and neuropathy. Hyperglycemia leads to generation of reactive oxygen species (ROS) and increases oxidative damage of lipids, DNA and proteins in many tissues. Oxidative stress is increased in cells in response to a depletion of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) that scavenge oxygen reactive species. Curcumin is the main component of Curcuma longa and has been used traditionally as an antidiabetic agent; and there are evidences that this substance presents high activity of ROS scavenger. Considering that diet is part of diabetic state treatment and that curcumin is considered and antioxidant agent, this study aimed to evaluate the effects of curcumin and/or insulin on oxidative stress parameters in streptozotocin-induced diabetic rats. In addition, it was performed a histopathological analysis of the liver and kidney of healthy and diabetic rats treated with these compounds. For this, the animals were divided into six groups, with six animals each: Control (C); Control/Curcumin (CCur); Diabetic/Saline (D); Diabetic/Insulin (DIns); Diabetic/Curcumin (DCur), and Diabetic/Insulin/Curcumin (DInsCur). Curcumin was diluted in corn oil and administered at the dosage of 60mg/kg once a day and insulin was administered twice a day, at the dosage of 1.5IU/rat in the morning and 2.5IU/rat in the afternoon, for a period of 30 days. In groups D and DCur, the histological analysis of the liver revealed elevated number of binucleated hepatocytes and alterations in hepatic trabeculae. In kidney there were vacuolization of tubular cells, glomerular congestion and mononuclear inflammatory focus. The treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. Thiobarbituric acid reactive substances (TBARS) levels were increased in serum of D and DInsCur groups and in hepatic and renal tissue of group D (P

Conselho Nacional de Desenvolvimento Científico e Tecnológico Cadmium (Cd) is one of the most toxic heavy metals by their ability to affect the vital organs like liver, kidney, brain and other. This metal can trigger a framework of oxidative stress by increase of reactive oxygen species and also affect cholinergic and purinergic neurotransmission. Quercetin (Querc), a flavonoid found in various foods has several functions in the body as a therapeutic antioxidant and neuroprotective action. The aim of this study was to evaluate the activity of ectoenzymes and acetylcholinesterase (AChE) activity in synaptosomes of the cerebral cortex of adult rats exposed to cadmium chloride at a dose of 2.5 mg/kg and treated with Querc at doses of 5, 25 and 50mg/kg, both solutions were orally administered in a volume of 1 mL/kg for 45 days. Results showed that the hydrolysis of ATP, ADP, AMP and ADA activity in the synaptosome cerebral cortex in the Cd/ethanol group increased compared to the saline/ethanol group (p

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Cigarette smoke is a serious health problem and the most important cause of avoidable death in the world. It has a complex mixture with more than 4700 constituents, including nicotine and reactive oxygen species (ROS). The most common cause of its toxicity is the atherosclerosis and lipid peroxidation being nicotine an immunosuppressant compound. Among the major cellular changes promoted by nicotine is the disorder in the aggregation of platelets, which participate in the regulation of thromboembolic processes releasing nucleotides such as adenosine diphosphate (ADP). Once exerted the signaling events the nucleotides are degraded by the action of the enzymes NTPDase, 5´- nucleotidase and adenosine deaminase (ADA). This purinergic cascade of enzymatic hydrolysis is also present in lymphocytes and supplies a great amount of signaling modulating the immune system. Another important signaling molecule is acetylcholine (ACh) which is quicklys hydrolyzed by acetylcholinesterase (AChE) and is associated with the cognition process. The first hypothesis to be tested in this study was to investigate the activity of ectonucleotidases in platelets and the ADA from plasma of rats exposed to cigarette smoke during four weeks. The results in platelets demonstrated an increase for adenosine triphosphate (ATP), ADP, adenosine monophosphate (AMP) hydrolysis and adenosine deamination. These results suggest a compensatory organic response to regulate the evels of adenosine, a powerful inhibitor of platelet aggregation and important modulator of vascular tone. The second hypothesis was studied in vivo and in vitro the hydrolysis of nucleotides and nucleosides in lymphocytes of rats submitted to nicotine exposure per se. The in vivo results of lymphocytes demonstrated a decrease in the hydrolysis of ATP, ADP and adenosine in the concentrations of 0.25 and 1.0 mg/kg of nicotine. The expression of NTPDase protein and the counting of lymphocytes in rats were also diminished after nicotine exposure. The quantification of nucleotides and nucleoside in serum of rats treated with nicotine in the dose of 0.25 mg/kg showed an increase in the ATP (39%), ADP (39%) and adenosine (303%) levels. For the in vitro study the ATP-ADP-adenosine hydrolysis were diminished by nicotine in the nicotine concentrations tested (1 mM, 5 mM, 10 mM and 50 mM). These results suggest that alterations in the activity and expression of these enzymes in lymphocytes can contribute for the understanding of the mechanisms involving the suppression of the immune system caused by nicotine. Finally, the third hypothesis was to investigate the activity of AChE and the level of lipid peroxidation in striatum, cerebral cortex, hippocampus, and cerebellum of rats exposed to cigarette smoke and treated with vitamin E (50 mg/kg/day) during four weeks. The results had demonstrated an increase in the activity of AChE and in the levels of lipid peroxidation in the striatum, cerebral cortex and cerebellum, suggesting that this type of exposition can affect the functionality of the cholinergic system and increase the oxidative damage in the central nervous system (SNC). In addition, vitamin E was capable to reverse these increases, suggesting the use of this antioxidant compound in this type of exposition. Moreover, this study also suggests that cigarette smoke and nicotine modulate the purinergic system of platelets and lymphocytes, which may lead the propensity of thromboembolic and immunosuppressant illnesses, with mobilization of the phisiological defenses for a compensatory response. A fumaça de cigarro é um grave problema de saúde e a mais importante causa de morte evitável no mundo. Possui uma complexa mistura com mais de 4000 constituintes, incluindo a nicotina e compostos que geram espécies reativas de oxigênio (EROs) no organismo. A causa mais comum de sua toxicidade é a aterosclerose e a peroxidação lipídica sendo a nicotina um composto imunossupressor. Entre as alterações celulares causadas pela nicotina, destacam-se os distúrbios na agregação de plaquetas e estas participam da regulação nos processos tromboembólicos, pela liberação de nucleotídeos tais como a adenosina difosfato (ADP). Uma vez exercido os eventos de sinalização os nucleotídeos são degradados pela ação das enzimas NTPDases, 5´-nucleotidase e adenosina desaminase (ADA). Esta cascata enzimática de hidrólise das purinas também está presente nos linfócitos e fornece um grande leque de sinalizações modulando a resposta imune. Outra molécula importante de sinalização é a acetilcolina (ACh) que é rapidamente hidrolisada pela acetilcolinesterase (AChE) e está associada ao processo de cognição. A primeira hipótese a ser testada neste estudo foi investigar a atividade das ectonucleotidases em plaquetas e a ADA no plasma de ratos expostos à fumaça de cigarro por quatro semanas. Os resultados em plaquetas demonstraram um aumento para a hidrólise de adenosina trifosfato (ATP), ADP, adenosina monofosfato (AMP) e adenosina. Esses resultados sugerem uma resposta orgânica compensatória com objetivo de manter os níveis de adenosina, um potente inibidor da agregação plaquetária e importante modulador do tônus vascular. A segunda hipótese foi realizar estudos in vivo e in vitro da hidrólise de nucleotídeos e nucleosídeos em linfócitos de ratos submetidos a exposição à nicotina per se. Os resultados in vivo de linfócitos demonstraram um decréscimo da hidrólise de ATP, ADP e adenosina nas concentrações de nicotina de 0,25 e 1,0 mg/kg. A expressão da proteína NTPDase e a contagem de linfócitos em ratos também foram diminuídas pela nicotina. A determinação dos níveis de nucleotídeos e nucleosídeos no soro de ratos tratados com nicotina na dose de 0,25 mg/kg aumentou para o ATP (39%), o ADP (39%) e a adenosina (303%). Para o estudo in vitro a hidrólise de ATP-ADP-adenosina foi diminuída pelas concentraçoes de nicotina (1 mM, 5 mM, 10 mM e 50 mM). Estes resultados sugerem que alterações na atividade e expressão destas enzimas nos linfócitos pode contribuir para a compreensão dos mecanismos envolvendo a supressão da resposta imune causada pela nicotina. Por fim, a terceira hipótese, foi investigar a atividade da AChE e o nível de peroxidação lipídica no estriado (ES), no córtex cerebral (CC), no hipocampo (HC) e no cerebelo (CE) de ratos expostos à fumaça de cigarro e tratados com vitamina E (50 mg/kg/dia) por quatro semanas. Os resultados demonstraram um aumento na atividade da AChE e no nível de peroxidação lipídica no ES, no CC e no CE, sugerindo que este tipo de exposição pode afetar a funcionalidade do sistema colinérgico e aumentar os danos oxidativos no sistema nervoso central (SNC). Em adição, a Vitamina E foi capaz de reverter estes efeitos, o que sugere uma boa escolha de terapia com este antioxidante neste tipo de exposição. Alem disso, este estudo também pode sugerir que a fumaça de cigarro e a nicotina modulam o sistema purinérgico de plaquetas e linfócitos, o que pode levar a propensão de doenças tromboembólicas e imunossupressoras, com a mobilização das defesas do organismo para uma resposta compensatória.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Sporotrichosis is a subcutaneous fungal infection of evolution subacute or chronic, inflammatory lesions characterized by pyogranulomatous aspect, caused by the dimorphic fungus Sporothrix schenckii. Adenosine deaminase (ADA) is a key enzyme in the purine metabolism, promoting the deamination of adenosine, an important anti-inflammatory molecule. The increase in ADA activity has been demonstrated in several inflammatory conditions, however, no data in the literature associated with this fungal infection. The objective of this study was to evaluate the activity of serum ADA (S-ADA) and lymphocytes (L-ADA) of rats infected with S. schenckii. We used seventy-eight rats divided into two groups. In the first experiment, rats were infected subcutaneously and in the second experiment, infected intraperitoneally. Blood samples for hematologic evaluation and activities of S-ADA and ADA-L were performed on days 15, 30 and 40 post-infection (PI) to assess disease progression. In experiment II, was observed in an acute decrease in activity of S-ADA and L-ADA (p

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Inflammatory and degenerative pathophysiological processes within the central nervous system (CNS) and platelets are important causes of human disease promoted by cigarette smoke. The objective of the present study was to evaluate activity of the enzymes that hydrolyze nucleotides and nucleosides in synaptosomes of cerebral cortex and platelets from rats exposed to aged and sidestream diluted smoke of commercial cigarettes. The animals were randomly divided into two groups (ten rats in each group): control (not exposed to cigarette smoke) and smoke (exposed to cigarette smoke). The smoke group was exposed via inhalation through the nose only 15 minutes per day inside a cigarette smoke exposure chamber during 3 weeks. The results demonstrated that E-NTPDase (with ATP and ADP as substrate) activity was significantly higher in the smoke group (p