Staphylococcus aureus is one of the major causes of food-borne pathogenesis. Antibiotic consumption for these pathogens has been increasing year by year world-wide. In order to decrease the use of synthetic antibiotics, fresh fruits and dry herbs consumed as beverages in regular diets were examined as potential natural antibiotics for the treatment of food based infections against Staphylococcus aureus. Herbs consumed as tea infusions including Pimpinella anisum L. (anise), Anthemis arvensis L. (camomile), Rosa canina L. (rosehip), Salvia fruticosa Mill (sage) and fresh fruit juices including Vitis vinifera L. (grape), Citrus sinensis L. (orange), Prunus persica L. (peach) and Punica granatum L. (pomegranate) were selected as samples of hot or cold consumed beverages in our daily diets. Extracts of fresh fruit juices were prepared in methanol, on the other hand, tea infusions of herbs were filtered and lyophilized. Antioxidant capacities of the plant samples were investigated by radical scavenging methods, namely 2&rsquo / 2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as determination of total phenolic and flavonoid contents. Furthermore, antimicrobial activities of plant samples were determined by minimum inhibitory concentration and minimum bactericidal concentration methods along with disc diffusion method. Trolox equivalent antioxidant capacities (TEAC) of the herbal tea infusions obtained by ABTS radical scavenging method were ranged between 48.38 &plusmn / 1.242 and 715.73 &plusmn / 4.265 (&mu / mol Trolox equivalent (TE)/g of extract) while, TEAC values of fresh fruits juices were between 26.86 &plusmn / 0.217 and 73.55 &plusmn / 0.973 (&mu / mol Trolox equivalent (TE)/g of extract). Moreover, EC50 values of the tea infusions obtained by DPPH radical scavenging method were ranged between 0.05 &plusmn / 0.001 and 1.53 &plusmn / 0.004 (mg/mL) while, EC50 values of the fruit juices were 1.6 &plusmn / 0.014 and 2 &plusmn / 0.093 (mg/mL). Total phenolic content of the plant samples tested in this study were varied from 1.383 (&mu / g gallic acid equivalent (GAE)/mg of extract) to 159.167 (&mu / g gallic acid equivalent (GAE)/mg of extract) and total flavonoid content varied from 0.111 (&mu / g quercetin equivalent (QE)/mg of extract) to 201.15 (&mu / g quercetin equivalent (QE)/mg of extract). Sage, orange and grape displayed higher antimicrobial activities with values of 1.5, 6 and 6 mg/mL minimum inhibitory concentrations and 1.5, 24 and 24 mg/mL minimum bactericidal concentrations, respectively. Inhibition zone diameters of sage, orange and grape were found to be 9, 9 and 11 mm.

No description available.

Type II diabetes mellitus (T2D) and Alzheimer's disease (AD) share aetiology and have a high incidence of co-morbidity. Evidence suggests that both diseases are caused by the pathogenic aggregation of an intrinsically disordered native amyloid peptide. Furthermore, T2D and AD share risk factors such as age, obesity and vascular health. Recent studies demonstrate that amylin, an amyloidogenic pancreatic hormone deposited in the pancreas in T2D, is also deposited in the brain in AD. We hypothesised that amylin directly contributes to AD through deposition in the brain and activation of pathogenic signalling cascades. We provide evidence to validate that amylin is deposited in the brain parenchyma and vasculature. Furthermore, we present data demonstrating amylin (IAPP) expression in the brain is significantly elevated in AD; and that amylin treatment increases amyloid-beta (AB) secretion in neuronal culture. Soluble oligomeric species of AB cause AD by initiation of downstream signalling cascades that dysregulate kinase activity, promote tau phosphorylation and result in neuronal death. One such pathway involves AB oligomer activation of the Src-family kinase Fyn, through binding to the cellular prion protein (PrPC) receptor complex. We provide evidence that amylin activates Fyn in neuroblastoma and stem cell derived neurons, this activation is possibly mediated through PrPC. Together the data presented in this thesis demonstrate multiple modes of action whereby amylin may directly propagate or indirectly exacerbate AD-associated processes. Amylin aggregation, deposition, up-regulation and signalling should be considered one of several links between T2D and AD. The pathogenic actions of AB and amylin are mediated by oligomer species. Therefore therapeutics which prevent oligomerisation or oligomer action may be valuable in AD and T2D. One such class of therapeutic are flavonoids. Our collaborators have recently demonstrated the flavonoids rutin and quercetin reduce amylin aggregation and extend lifespan in diabetic animal models. As a result of this we investigated the anti-amyloidogenic and anti-oligomeric properties of the flavonoid quercetin against AB. Quercetin treatment prevented AB oligomerisation, cell binding of pre-formed AB oligomers and also reduced APP processing in cell models. These data suggest quercetin is a multimodal therapeutic with potential utility in AD and T2D and should be explored for further drug development.

This work concentrated on isolation of novel hop transcription factors from bHLH, bZIP, MYB, and WRKY families involved in the regulation of lupulin flavonoid pathways, followed by their structural and functional analysis. Structural analyses included bioinformatic approaches to elucidate gene organization, domain structure of the putative protein products, and potential post-translational modifications. I performed site-directed mutagenesis to disclose the role of phosphorylation sites in HlbZIP1A stability. Further, this work determined protein-DNA interactions for obtained TFs, giving support to the binding of MYB-bHLH-WDR complexes to the promoter of chalcone synthase H1, a key enzyme of the lupulin flavonoid pathways. Employing bioinformatic approaches, quantitative RT-PCR and transient co-expression, I pointed out chalcone synthase H1 as a regulatory crossroads in the metabolic (flavonoid) responses during hop stunt viroid pathogenesis.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Silver catfish, Rhamdia quelen, is one of the most cultivated fish species in southern Brazil. Products destined for improving rearing and production of this species are required due to its importance for aquaculture. Oxidative stress (OS) is one of the main challenges in fish culture, so the use of compounds with antioxidant capacity may be valuable. The flavonoid rutin has several beneficial effects and represents an important alternative to reduce the physiological changes that arise from rearing-related stress. This study evaluated the influence of three diets containing rutin (0, 0.15 and 0.30 % rutin) on blood parameters and the antioxidant response of silver catfish. After a 21-day feeding period, blood was withdrawn for biochemical analysis and determination of plasma cortisol levels. The fish were then euthanized for sampling of the brain, gills, liver, kidney and muscle. Biomarkers of OS, thiobarbituric reactive substances (TBARS), lipid hydroperoxides (LOOH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), content of non-protein thiol groups (NPSH), content of ascorbic acid (AA) and total antioxidant capacity (TRAP) were determined. Fish fed the diet having 0.15 % rutin had lower cortisol levels compared to control. Nonetheless, the diet with rutin did not affect the hematological parameters. The levels of lipid peroxidation measured by determination of TBARS and LOOH in the brain, gills, liver and muscle decreased in the fish fed the diet containing rutin; in the kidney, however, only the levels of LOOH were reduced in these fish. When compared to control, the rutin-enriched diet increased the activity of SOD, CAT, NPSH content, AA and TRAP in the brain, GST and TRAP in the gills, SOD, CAT, GST, NPSH content, AA and TRAP in the liver, CAT, GST and TRAP in the kidney, and GPx, NPSH content, AA and TRAP in the muscle. In conclusion, these results suggest that rutin supplementation in silver catfish diet is recommended because it increases the tissue antioxidant response, thus preventing oxidative damage. / O jundiá, Rhamdia quelen, é uma das espécies mais cultivadas no sul do Brasil. Produtos destinados a melhorar o cultivo e produção do jundiá são necessários devido à importância desta espécie para a aquicultura. O estresse oxidativo (OS, do inglês oxidative stress) é um dos principais desafios no domínio da piscicultura, portanto a utilização de compostos com capacidade antioxidante pode ser útil. O flavonoide rutina tem vários efeitos benéficos e torna-se uma alternativa importante a fim de reduzir as alterações fisiológicas resultantes do estresse atrelado ao cultivo. Este estudo avaliou a influência de três dietas contendo a rutina (0, 0,15 e 0,30 % rutina) sobre os parâmetros sanguíneos e resposta antioxidante em jundiás. Após um período de 21 dias de alimentação, o sangue foi coletado para a análise sanguínea. Os peixes foram então eutanasiados para amostragem do encéfalo, brânquias, fígado, rim e músculo. Uma alíquota de sangue foi amostrada para a análise bioquímica e do cortisol plasmático. Os biomarcadores de OS, substâncias que reagem ao ácido tiobarbitúrico (TBARS), hidroperóxidos lipídicos (LOOH), superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa S-transferase (GST), o conteúdo dos grupos tióis não proteicos (NPSH), conteúdo de ácido ascórbico (AA) e a capacidade antioxidante total (TRAP) foram determinados. Os peixes que receberam a dieta contendo 0,15 % rutina apresentaram níveis de cortisol mais baixos do que o controle. No entanto, a dieta contendo rutina não influenciou os parâmetros hematológicos. Os níveis de lipoperoxidação medidos por determinação de TBARS e LOOH no encéfalo, brânquias, fígado e músculo diminuíram nos peixes que receberam a dieta contendo rutina; exceto no rim onde houve apenas a redução dos níveis de LOOH em todas as dietas. Quando comparado ao controle, a dieta enriquecida com rutina aumentou a atividade da SOD, CAT, o conteúdo de NPSH, AA e TRAP no encéfalo, GST e TRAP nas brânquias, SOD, CAT e GST, o conteúdo de NPSH, AA e TRAP no fígado, CAT, GST e TRAP no rim, GPx, conteúdo de NPSH, AA e TRAP no músculo. Em conclusão, estes resultados sugerem que a suplementação contendo rutina na dieta do jundiá é recomendada pois aumenta a resposta antioxidante no tecido, evitando o dano oxidativo.

Made available in DSpace on 2015-05-14T12:59:49Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2147842 bytes, checksum: 4096aadcaa77b162c3d6533c50132e36 (MD5) Previous issue date: 2012-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The genus Piptadenia Benth. part of the Mimosoideae subfamily which is included to the Fabaceae family, the third largest family of angiosperms, widely distributed, being one of the largest in dicotyledonous and economic importance. Piptadenia stipulacea is widely distributed in the caatinga biome, and is used in popular medicine to treat inflammation, activity that has been proven pharmacologically. This paper aims to continue the chemical knowledge of P. stipulacea. The chemical compounds were identified using analysis of data obtained by spectroscopic methods, such as 1H and 13C NMR uni- and bidimensional. The phytochemical study of chloroform phase resulted in the isolation of two flavonoids: 3,3',5,7-tetrahydroxy-4 ,6-dimethoxyflavone and 4 ,5,7- trihydroxy-3 ,6-dimethoxyflavone, both previously described in the species, of ethyl acetate phase resulted in the isolation of a mixture of two novel flavonoids in the species (5,7,4 -trihydroxy-6-methoxyflavone e 3,5,7,4 -tetrahydroxyflavonol), whereas the remaining hydroalcoholic phase resulted in the isolation of an indolic alkaloid: methyl(2-{3-[2-(methylamino)ethyl]-1H-indol-1-yl}ethyl)amine, firstly described in the literature. / O gênero Piptadenia Benth. faz parte da subfamília Mimosoideae a qual pertence à família Fabaceae, a terceira maior família das angiospermas, de ampla distribuição geográfica, sendo uma das maiores em dicotiledôneas e de importância econômica. Piptadenia stipulacea apresenta ampla distribuição no bioma da caatinga nordestina, sendo utilizada na medicina popular no tratamento das inflamações, atividade esta, já comprovada farmacologicamente. O presente trabalho tem o objetivo de dar continuidade ao conhecimento químico de P. stipulacea. Os contituintes químicos isolados foram identificados por meio da análise de dados obtidos por métodos espectroscópicos, tais como RMN de 1H e 13C uni e bidimensionais. O estudo fitoquímico da fase clorofórmica resultou no isolamento de dois flavonoides: 3,3 ,5,7-tetrahidroxi-4 ,6-dimetoxiflavona e 4 ,5,7-trihidroxi-3 ,6-dimetoxiflavona, ambos já descritos na espécie, da fase acetato de etila uma mistura de dois flavonoides inéditos na espécie (5,7,4 trihidroxi-6-metoxiflavona e 3,5,7,4 -tetrahidroxi-6-flavonol) enquanto que, da fase hidroalcoolica remanescente resultou no isolamento de um alcaloide indólico: N-metil-indol-1,3-etanamina, descrito pela primeira vez na literatura.

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2017-10-24T12:45:23Z No. of bitstreams: 1 PDF - Isabelly da Silva Venâncio de Macêdo.pdf: 21766192 bytes, checksum: 18670653de69a62d3b2eb439387816e8 (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2017-10-26T16:55:33Z (GMT) No. of bitstreams: 1 PDF - Isabelly da Silva Venâncio de Macêdo.pdf: 21766192 bytes, checksum: 18670653de69a62d3b2eb439387816e8 (MD5) / Made available in DSpace on 2017-10-26T16:55:33Z (GMT). No. of bitstreams: 1 PDF - Isabelly da Silva Venâncio de Macêdo.pdf: 21766192 bytes, checksum: 18670653de69a62d3b2eb439387816e8 (MD5) Previous issue date: 2017-03-07 / In recent decades to expand the development of nutraceuticals from the use of plants containing active metabolites for the support not treating various diseases.The rutin is a naturally occurring flavonoid widely known to exhibit a variety of pharmacological activities, such as antioxidant, antiplatelet and antitumor agonist making it a promising candidate for nutraceuticals for chemoprevention purposes. However, its low solubility in aqueous media hinders its permeation in biological systems, thus reducing its therapeutic activity. The development of solid dispersions has been shown to be an effective technique for promoting the increase of aqueous solubility of drugs. The aim of this work was to produce solid dispersion microparticles of rutin, aiming to increase their aqueous solubility. The microparticles were produced by spray-drying using a Box-Behnken factorial design. It was used as carrier polyvinylpyrrolidone (PVP K-30) and for drying colloidal silicon dioxide (Aerosil® 200). The variables of the process studied were the temperature, percentage of rutin and the percentage of Aerosil, totaling 15 experiments. Physical mixtures of the active compound with adjuvants in 1: 1 and 1:9 ratios were also prepared. The results obtained were analyzed by the surface response technique (ANOVA). The evaluated parameters, besides the aqueous solubility, were yield, moisture content, solubility, dissolution in vitro. The microparticles as well as the physical mixtures were characterized by thermal analysis techniques: differential thermal analysis and thermogravimetry, X-ray diffraction and scanning electron microscopy. Statistical analysis showed that the yield was influenced by only one variable, while the moisture content was influenced directly by temperature in combination with the percentage of aerosil. The microparticles showed good yield (31% - 52%) and low moisture content (lessthan 2%). Regarding the solubility, there was no significant change between the microparticles related to the studied parameters. However, there was a significant increase in the solubility of the microparticles when related to the pure drug, with a solubility increase of up to 9 times, besides the excellent increase in the dissolution profile of the drug. Regarding thermal analysis and complementary techniques, the results showed good thermal and physical stability profile of the microparticles. Therefore, the development of microparticulate solid dispersions containing rutin by spray drying was able to increase the solubility of this flavonoid, making it a potential candidate as a nutraceutical for use in complementary diets. / Nas últimas décadas tem se expandido o desenvolvimento de nutracêuticos a partir da utilização de plantas que contém metabólitos ativos para suporte no tratamento de diversas doenças. A rutina é um flavonoide natural extensamente conhecido por apresentar variedade de atividades farmacológicas como, por exemplo, antioxidante, anti-agregante plaquetária e antitumoral tornando-a um promissor candidato a nutracêutico para fins de quimioprevenção. Entretanto, sua baixa solubilidade em meio aquoso dificulta sua permeação nos sistemas biológicos diminuindo assim sua atividade terapêutica. O desenvolvimento de dispersões sólidas tem se mostrado como uma técnica eficaz para a promoção do incremento da solubilidade aquosa de fármacos. Esse trabalho teve como objetivo produzir micropartículas de dispersão sólida de rutina visando o incremento de sua solubilidade aquosa. As micropartículas foram produzidas por spray-drying usando um planejamento fatorial Box-Behnken. Foi usando como carreador polivinilpirrolidona (PVP K-30) e para secagem dióxido de silício coloidal (Aerosil® 200) . As variáveis do processo estudas foram a temperatura, porcentagem de Rutina e a porcentagem do Aerosil, totalizando 15 experimentos. Foram preparadas também misturas físicas do ativo com os adjuvantes nas proporções 1:1 e 1:9. Os resultados obtidos foram analisados pela técnica de superfície de resposta (ANOVA). Os parâmetros avaliados, além da solubilidade aquosa, foram rendimento, teor de umidade, solubilidade, dissolução in vitro. As micropartículas assim como as misturas físicas foram caracterizadas pelas técnicas de análise térmica: análise térmica diferencial e termogravimetria, difração de raios X e microscopia eletrônica de varredura. A análise estatística demonstrou que o rendimento sofreu influência de apenas uma variável, enquanto que o teor de umidade sofreu influência direta da temperatura em combinação com a porcentagem de aerosil. As micropartículas apresentaram bom rendimento (31% – 52%) e baixo teor de umidade (inferior a 2%). Quanto a solubilidade não houve alteração significativa entre as micropartículas relacionada aos parâmetros estudados. Porém, houve um aumento significativo da solubilidade das micropartículas quando relacionado ao fármaco puro, com incremento de solubilidade de até 9 vezes, além do excelente aumento no perfil de dissolução do fármaco. Com relação a análise térmica e técnicas complementares os resultados mostraram bom perfil de estabilidade térmica e física das micropartículas. Portanto, o desenvolvimento de dispersões sólidas microparticuladas contendo rutina por spray drying foi capaz de aumentar a solubilidade desse flavonóide, tornando-o um potencial candidato como nutracêutico para ser usado em dietas complementares.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Marcetia macrophylla à um planta endÃmica da Bahia pertencente à famÃlia Melastomataceae. O extrato hidroalcoÃlico das folhas de M. macrophylla foi submetido a sucessivas cromatografias resultando no isolamento e identificaÃÃo de seis metabÃlitos secundÃrios: o triterpeno esqualeno, a mistura esteroidal β-sitosterol e estigmasterol, o flavonÃide quercetina, a isoflavona 4â,5,7-trihidroxi-6,8-dimetilisoflavona e o derivado do Ãcido gÃlico, galato de etila. Os metabÃlitos foram isolados atravÃs de mÃtodos cromatogrÃficos clÃssicos, tais como: cromatografia de adsorÃÃo em coluna, partiÃÃo lÃquido-lÃquido e cromatografia de exclusÃo. A elucidaÃÃo estrutural foi efetuada atravÃs dos mÃtodos espectroscÃpicos IV, EM e RMN 1H e 13C, uni e bidimensional, e comparaÃÃo com os dados descritos na literatura. Este à o primeiro relato do estudo fitoquÃmico de M. macrophylla. / Marcetia macrophylla is an endemic plant of Bahia belonging to the Melastomataceae family. The hydroalcoholic extract of Marcetia macrophylla leaves was subjected to successive chromatographic analysis to afford six secondary metabolites: the triterpene squalene, the steroidal mixture of β-sitosterol and stigmasterol, the flavonoid quercetin,the isoflavone 4',5,7-trihydroxy-6,8-dimethylisoflavone and the gallic acid derived, ethyl gallate. The metabolites were isolated by conventional chromatographic methods such as adsorption column chromatography, liquid-liquid partition and exclusionchromatography. The identification of these compounds was possible by IR, MS and 1H and 13C NMR, uni and bidimensinal, and comparison with literature data. This is the first report of phytochemical studies of Marcetia macrophylla.

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No. of bitstreams: 1 Dissertação - Priscila Moraes dos Santos.pdf: 3531569 bytes, checksum: 1addf55099b28e0cfbe42b2e94a1e935 (MD5) Previous issue date: 2013-07-13 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Species of the genus Bauhinia are used in various parts of the world to treat various diseases, especially for the treatment of diabetes due to hypoglycemic activity has proven to Bauhinia forficata species, which is associated with the presence of the flavonoid kaempferitrina. However, other species also have the same effect and this is associated with the presence of other flavonoids glycosides. In this study we sought to prepare the phytochemical profile of four species of Bauhinia Amazon region from their crude extracts, alkaloid and flavonoics fractions in order to promote an initial scan for more specific biotechnology projects. Furthermore, Bauhinia coronata (Manaus-AM), B. purpurea (Manaus-AM), B. acreana (Manacapuru-AM) and B. purpurea (S. Gabriel da Cachoeira) were analyzed for antioxidant activity front free radicals DPPH., ABTS.+ and O2-, as well as the inhibition of enzymes lipoxygenase, α-amylase, lypase, α-glycosidase and tyrosinase. Among these assays as biological antioxidants and tyrosinase and α-glycosidase, stood the species B. coronata and B. purpurea with lower values for IC50 (IC50 of B. coronata leaf’s crude extract: 1.91 ± 0.55 μg / mL). The toxicity of crude extracts was also tested against Artemia salina, with LD50 values of greater than 250 μg/mL, indicating the low toxicity of them. However, the analysis of their potential cytotoxic and antibacterial no species has been active, which is contrary to reports in the literature that Bauhinia purpurea was mentioned with these potentials. The profile of flavonoids were identified, using TLC, HPLC-DAD-UV and mass spectrometry, and the rutin and isoquercitrin flavonoids in the species B. coronata and B. purpurea, the latter being related to the flavonoid has hypoglycemic activity of other species of Bauhinia, and anti-inflammatory action. The kaempferitrin flavonoid wasn’t found in any species, as no substance of the alkaloidal class. The results from the antioxidant activity, low toxicity and the presence of flavonoids with potential herbal stimulate future research for specific biotechnological purposes. / Espécies do gênero Bauhinia são utilizadas em diversas partes do mundo para tratamento de diversas doenças, principalmente para o tratamento da diabetes, devido a atividade hipoglicemiante já comprovada para a espécie Bauhinia forficata, a qual é associada à presença do flavonoide kaempferitrina. Entretanto, outras espécies também apresentam o mesmo efeito e a este é associada a presença de outros flavonoides glicosilados. Neste trabalho buscou-se elaborar o perfil fitoquímico de quatro espécies de Bauhinia da Região Amazônica a partir de seus extratos brutos, frações flavonoídicas e alcaloídicas, a fim de promover uma varredura inicial para projetos biotecnológicos mais específicos. Além disso, Bauhinia coronata (Manaus-AM), B. purpurea (Manaus-AM), B. acreana (Manacapuru- AM) e B. purpurea (S. Gabriel da Cachoeira) foram analisadas para determinação do potencial antioxidante frente os radicais livres DPPH., ABTS.+ e O2-, assim como a inibição de enzimas lipoxigenase, α-amilase, lipase, α-glicosidase e tirosinase. Dentre estes ensaios antioxidantes e biológicos como tirosinase e α-glicosidase, destacaram-se as espécies B. coronata e B. purpurea com os valores mais baixos para CI50 (CI50 do extrato bruto de folha de B. coronata: 1,91±0,55 μg/mL) . A toxicidade dos extratos brutos também foi testada frente ao microcrustáceo Artemia salina, com valores de DL50 superiores a 250 μg/mL, indicando a baixa toxicidade dos mesmos. Entretanto, na análise do seu potencial citotóxico e antibacteriano nenhuma espécie foi ativa, o que é contrário aos relatos da literatura em que a Bauhinia purpurea já foi mencionada com estes potenciais. No perfil de flavonoides foram identificados, utilizando CCD, CLAE-DAD-UV e espectrometria de massas, os flavonoides rutina e isoquercitrina nas espécies B. coronata e B. purpurea, sendo este último flavonoide já relacionado à atividade hipoglicemiante de outras espécies de Bauhinia, além de ação antiinflamatória. O flavonoide kaempferitrina não foi encontrado em nenhuma espécie, como nenhuma substância relativa à classe alcaloídica. Os resultados obtidos a partir da atividade antioxidante, baixa toxicidade e a presença de flavonoides com potencial fitoterápico estimulam futuras pesquisas específicas para fins biotecnológicos.

Submitted by Neusa Fagundes (neusa.fagundes@unioeste.br) on 2018-03-06T19:51:35Z No. of bitstreams: 2 Suélyn_Koerich2017.pdf: 1381882 bytes, checksum: 2404add8c5fc58aba0ebaa970b5c23be (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-03-06T19:51:36Z (GMT). No. of bitstreams: 2 Suélyn_Koerich2017.pdf: 1381882 bytes, checksum: 2404add8c5fc58aba0ebaa970b5c23be (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-12-15 / Fundação Araucária / Tamoxifen is classified as selective estrogen receptor modulador (SERM), being used in the treatment and prevention of breast cancer. Although presents many side effects, tamoxifen is a therapy of choice for the treatment of breast cancer in the postmenopausal period. The quercetin, a flavonoid with antioxidant potent effect, has benefits on the adverse effects caused by tamoxifen, especially those related to lipoperoxidation. The study of the neuroprotective effect of quercetin on brain bioenergetics is important for the recognition of the mechanisms involved. Thus, the objective of this work was to analyze the tamoxifen effects on glucose metabolism in the brain and the influence of quercetin coadministered with tamoxifen on passage of glucose from the cerebrospinal fluid to the brain of ovariectomized rats submitted to tamoxifen treatment. For this, bilaterally ovariectomized rats were separated into groups and treated with canola oil (1.0 mL.Kg-1) tamoxifen (5 mg.Kg-1), quercetin (22.5 mg.Kg-1) and the coadministration of tamoxifen (5 mg.Kg-1) plus quercetin (22.5 mg.Kg-1), orally for 14 days. The blood, cerebrospinal fluid, cerebellum, cortex, and hippocampus were collected for glucose lactate and pyruvate dosage as well copper and ceruloplasmin. It was observed that tamoxifen increased blood glucose levels and that co-administration with quercetin brought these levels close to the values of the control group. In cerebrospinal fluid, the quercetin administration didn´t influence glucose levels and in the different brain regions, both quercetin alone such as coadministration with tamoxifen significantly decreased glucose values when compared to the group that received only tamoxifen. The coadministration of quercetin with tamoxifen was shown be effective not only in maintenance glycemic levels but also in cerebral glucose levels. / O tamoxifeno é classificado como modulador seletivo de receptor de estrógeno (SERM), sendo utilizado no tratamento e na prevenção do câncer de mama. Embora apresente muito efeitos colaterais, o tamoxifeno é a terapia de escolha para o tratamento do câncer de mama no período da pós-menopausa. A quercetina, um flavonóide com potente efeito antioxidante, traz benefícios diante dos efeitos adversos gerados pelo tamoxifeno, principalmente aqueles relacionados à lipoperoxidação. O estudo do efeito neuroprotetor da quercetina sobre a bioenergética cerebral é importante para o reconhecimento dos mecanismos envolvidos. Assim, o objetivo deste trabalho foi analisar o efeito do tamoxifeno sobre o metabolismo da glicose no cérebro e a influência da quercetina coadministrada com o tamoxifeno na passagem da glicose do líquido cefalorraquidiano para o cérebro de ratas ovariectomizadas submetidas ao tratamento com tamoxifeno. Para isso, ratas ovariectomizadas bilateralmente foram separadas em grupos e tratadas com óleo de canola (1,0 mL. Kg-1), (tamoxifeno (5 mg.kg-1), quercetina (22,5 mg.kg-1) e a coadministração de tamoxifeno (5 mg.kg-1) mais quercetina (22,5 mg.kg-1) por via oral, durante 14 dias. O sangue, o líquido cefalorraquidiano, o cerebelo, o córtex e o hipocampo foram coletados para a dosagem de glicose, lactato e piruvato, bem como cobre e ceruloplasmina. Foi observado que o tamoxifeno aumentou os níveis de glicose no sangue e que a coadministração com quercetina trouxe esses níveis próximos aos valores do grupo controle. No líquido cefalorraquidiano, a administração de quercetina não influenciou nos níveis de glicose e nas diferentes regiões do cérebro, tanto a quercetina isoladamente, como a coadministração da mesma com o tamoxifeno, diminuiu significativamente os valores de glicose, quando comparados ao grupo que recebeu apenas tamoxifeno. A coadministração de quercetina com o tamoxifeno mostrou-se eficaz não só na manutenção dos níveis glicêmicos, como também nos níveis de glicose cerebral.