Made available in DSpace on 2014-06-11T19:23:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-19Bitstream added on 2014-06-13T18:50:47Z : No. of bitstreams: 1 carvalho_fg_me_arafcf.pdf: 662906 bytes, checksum: b01eca6154c2a1b53dcdc4ffa1a8d2c8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Mulheres pós-menopausadas estão mais susceptíveis a problemas de saúde relacionados hipoestrogenismo, o que favorece ao processo de estresse oxidativo, inflamatório e ao desenvolvimento de doenças crônicas. Visto que a inclusão de cereais integrais na alimentação veicula componentes bioativos de efeito antioxidante e hipolipemiante, como as lignanas, o objetivo do presente estudo foi avaliar os efeitos hipolipemiantes, inflamatórios e antioxidantes de lignanas provenientes da ingestão de quinoa (Chenopodium quinoa) em um grupo de mulheres pós-menopausadas. Foi realizado um estudo prospectivo, randomizado, duplo cego e controlado por placebo, no qual participaram 35 mulheres que foram submetidas ao consumo diário de 25 gramas de quinoa em flocos ou placebo, no período de 4 semanas consecutivas. No início e ao final do tratamento, após as quatro semanas, foram realizadas avaliações antropométricas: peso corporal, estatura e circunferência da cintura; e coleta de sangue para a quantificação de glicose, colesterol total, LDL-C, HDL-C, triglicerídeos, marcadores de estresse (GSH e TBARS), Vitamina E, marcadores inflamatórios (IL-6 e TNF-α) e enterolignanas (END e ENL); e urina de 24 horas para quantificação de enterolignanas. Os resultados obtidos foram analisados em dois diferentes estudos os quais foram escritos na forma de artigo científico, sendo que o primeiro artigo abordou o efeito do consumo de quinoa sobre as concentrações de glicose, colesterol total e frações e de marcadores de estresse oxidativo, e o segundo artigo abordou o efeito das enterolignas sobre os marcadores inflamatórios em um grupo de mulheres pós-menopausadas. Ao comparar as dosagens no início e ao final do experimento, o presente estudo mostrou um possível efeito benéfico proveniente da ingestão do cereal quinoa, pois foram constatadas reduções significativas nas concentrações... / Postmenopausal women are more susceptible to health problems related to declining estrogen concentrations, which favor the oxidative stress and inflammatory process and the development of chronic diseases. Since daily consumption of grains involves bioactive components with an antioxidant and hypolipidemic effects, like lignans, the aim of the present study was to investigate the effect of quinoa consumption on the concentrations of glucose, total cholesterol and fractions, oxidative stress and inflammatory markers in a group of postmenopausal women. A prospective, randomized, double-blind and placebo-controlled study has been conducted on 35 women who had to consume 25 grams/day of quinoa flakes or placebo, over a period of 4 consecutive weeks. At the beginning and at the end of the intervention, after four weeks, anthropometric assessment was performed by body weight, height and abdominal circumference; and blood was collected for the determination of glucose, total cholesterol and fractions, oxidative stress and inflammatory markers, vitamin E and enterolignans, and 24-h urine was obtained for the determination of enterolignans. The results were analyzed in two different studies which were written in the form of a scientific paper, the first one emphasizes the effect of quinoa intake on consumption on the concentrations of glucose, total cholesterol and fractions, oxidative stress markers and in the second paper investigated the effect of enterolignans on inflammatory markers in a group of postmenopausal women. Comparing the beginning and the end of the intervention, the present study showed a possible beneficial effect by quinoa intake, because significant reductions were observed in serum triglycerides, TBARS and vitamin E concentrations, and an increase in enterolignan urinary excretion in the groups that consumed quinoa and placebo. A significant reduction of total cholesterol... (Complete abstract click electronic access below)

Enterolignans (enterodiol and enterolactone) exhibit structural similarity to estradiol and have therefore been hypothesized to modulate hormone related cancers such as breast cancer. The bioactivation of the plant lignan secoisolariciresinol diglucoside (SDG) requires the transformation by intestinal bacteria including the deglycosylation of SDG to secoisolariciresinol (SECO) followed by demethylation and dehydroxylation of SECO to enterodiol (ED). Finally, ED is dehydrogenated to enterolactone (EL). It is unclear whether the bacterial activation of SDG to ED and EL is crucial for the cancer preventing effects of dietary lignans. The possible protective effect of bacterial lignan transformation on a 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast cancer in gnotobiotic rats was investigated. Germ-free rats were associated with a defined lignan-converting consortium (Clostridium saccharogumia, Blautia producta, Eggerthella lenta, and Lactonifactor longoviformis). The rats colonized with lignan-converting bacteria consortium (LCC) were fed a lignan-rich flaxseed diet and breast cancer was chemical induced. Identically treated germ-free rats served as control. All bacteria of the consortium successfully colonized the intestine of the LCC rats. The plant lignan SDG was converted into the enterolignans ED and EL in the LCC rats but not in the germ-free rats. This transformation did not influence cancer incidence but significantly decreased tumor numbers per tumor-bearing rat, and tumor size. Cell proliferation was significantly inhibited and apoptosis was significantly induced in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERα and ERβ) and G-coupled protein receptor 30 (GPR30). Similar findings were observed for both insulin-like growth factor 1 (IGF-1) and epidermal growth factor receptor (EGFR) genes involved in tumor growth. Proteome analysis revealed that 24 proteins were differentially expressed in tumor tissue from LCC and germ-free. RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1) and poly(rC)-binding protein 1 (PBCP1) were down-regulated by 3.2- and 2.0-fold, respectively. These proteins are associated with cell proliferation. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione (non-enzymatic antioxidant) and malondialdehyde (oxidative stress marker) did not differ between the groups. In conclusion, the bacterial conversion of plant lignan to enterolignans beneficially influences their anti-cancer effect. However, the mechanisms involved in these effects remain elusive. / Enterolignanen (Enterodiol ED und Enterolacton EL) wird aufgrund ihrer strukturellen Ähnlichkeit zu Estradiol ein modulierender Einfluss auf hormonell bedingte Krebserkrankungen wie Brustkrebs nachgesagt. Das pflanzliche Lignan Secoisolariciresinoldiglucosid (SDG) wird durch Darmbakterien zum Enterolignan aktiviert. Dies erfolgt über dessen Deglykosylierung zu Secoisolariciresinol (SECO) gefolgt durch die Demethylierung und die Dehydroxylierung zu Enterodiol (ED). Schließlich wird ED zu Enterolacton (EL) dehydrogeniert. Es ist allerdings noch nicht bewiesen, dass die bakterielle Aktivierung von SDG zu ED und EL für die antikanzerogenen Wirkungen verantwortlich ist, die für dieses in der menschlichen Ernährung vorkommende Lignan beschrieben wurden. Um dies zu klären, wurde der Einfluss der bakteriellen Lignan-Transformation auf die Protektion gegenüber einem durch 7,12-Dimethylbenz(a)anthracen (DMBA)-induzierten Brustkrebs im gnotobiotischen Rattenmodell untersucht. Keimfreie Ratten wurden hierfür mit einem Konsortium aus vier Bakterienstämmen (Clostridium saccharogumia, Blautia producta, Eggerthella lenta, und Lactonifactor longoviformis) besiedelt, das die Umsetzung von SDG zu ED und EL katalysiert (LCC-Ratten). Ratten, die über den gesamten Versuchszeitraum keimfrei blieben, dienten als Kontrolle. Die Tiere wurden über 16 Wochen mit einer Leinsamen-Diät gefüttert, die reich an pflanzlichen Lignanen war. Während der Fütterung wurde bei allen Tieren Brustkrebs chemisch induziert. Das pflanzliche Lignan SDG wurde nur in den LCC Ratten zu den Enterolignanen ED und EL umgewandelt. Keimfreie Ratten zeigten keine Transformation von SDG. Die bakterielle Transformation von SDG hatte zwar keinen Einfluss auf die Inzidenz von Brustkrebs, jedoch verringerten sich durch die Besiedlung der Ratten mit SDG-transformierenden Bakterien die Anzahl von Tumoren pro tumortragender Ratte und die Tumorgröße deutlich. Zudem wurde die Zellproliferation in den LCC-Ratten deutlich gehemmt und die Apoptose induziert. Unterschiede in der Genexpression der Östrogenrezeptoren (ERα und ERß) und G-Protein-gekoppelte Rezeptoren (GPR30) wurden zwischen den LCC-Ratten und den Kontrolltieren nicht beobachtet. Ebenso verhielt es sich für die Gene des Insulinähnliche Wachstumsfaktoren 1 (IGF-1) und Epidermale Wachstumsfaktor rezeptoren (EGFR), welche in das Tumorwachstum involviert sind. Die Analyse des Proteoms des Tumorgewebes ergab 24 differentiell exprimierte Proteine zwischen keimfreien und LCC-Ratten. So wurden zum Beispiel die Proteine RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1) und poly(rC)-binding protein 1 (PBCP1), die mit der Zellproliferation assoziiert sind, in LCC-Ratten um das 3,2 bzw. 2,0-fache herunterreguliert. Die Aktivität ausgewählter antioxidativer Enzyme in Plasma und Leber war in den LCC-Ratten im Vergleich zu den keimfreien Tieren deutlich erhöht. Allerdings unterschieden sich die Konzentrationen von reduziertem Glutathion (nichtenzymatisches Antioxidans) und Malondialdehyd (oxidativer Stress-Marker) in Plasma und Leber nicht zwischen den beiden Besiedlungs-Gruppen. Zusammenfassend zeigen die Ergebnisse, dass die bakterielle Umwandlung von pflanzlichen Lignanen zu Enterolignanen deren antikanzerogene Wirkung entscheidend beeinflusst. Allerdings bleiben die zugrunde liegenden Mechanismen weiterhin ungeklärt.

Orientador: Anderson Marliere Navarro / Banca: Thaís Borges César / Banca: Telma Maria Braga Costa / Resumo: Mulheres pós-menopausadas estão mais susceptíveis a problemas de saúde relacionados hipoestrogenismo, o que favorece ao processo de estresse oxidativo, inflamatório e ao desenvolvimento de doenças crônicas. Visto que a inclusão de cereais integrais na alimentação veicula componentes bioativos de efeito antioxidante e hipolipemiante, como as lignanas, o objetivo do presente estudo foi avaliar os efeitos hipolipemiantes, inflamatórios e antioxidantes de lignanas provenientes da ingestão de quinoa (Chenopodium quinoa) em um grupo de mulheres pós-menopausadas. Foi realizado um estudo prospectivo, randomizado, duplo cego e controlado por placebo, no qual participaram 35 mulheres que foram submetidas ao consumo diário de 25 gramas de quinoa em flocos ou placebo, no período de 4 semanas consecutivas. No início e ao final do tratamento, após as quatro semanas, foram realizadas avaliações antropométricas: peso corporal, estatura e circunferência da cintura; e coleta de sangue para a quantificação de glicose, colesterol total, LDL-C, HDL-C, triglicerídeos, marcadores de estresse (GSH e TBARS), Vitamina E, marcadores inflamatórios (IL-6 e TNF-α) e enterolignanas (END e ENL); e urina de 24 horas para quantificação de enterolignanas. Os resultados obtidos foram analisados em dois diferentes estudos os quais foram escritos na forma de artigo científico, sendo que o primeiro artigo abordou o efeito do consumo de quinoa sobre as concentrações de glicose, colesterol total e frações e de marcadores de estresse oxidativo, e o segundo artigo abordou o efeito das enterolignas sobre os marcadores inflamatórios em um grupo de mulheres pós-menopausadas. Ao comparar as dosagens no início e ao final do experimento, o presente estudo mostrou um possível efeito benéfico proveniente da ingestão do cereal quinoa, pois foram constatadas reduções significativas nas concentrações... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Postmenopausal women are more susceptible to health problems related to declining estrogen concentrations, which favor the oxidative stress and inflammatory process and the development of chronic diseases. Since daily consumption of grains involves bioactive components with an antioxidant and hypolipidemic effects, like lignans, the aim of the present study was to investigate the effect of quinoa consumption on the concentrations of glucose, total cholesterol and fractions, oxidative stress and inflammatory markers in a group of postmenopausal women. A prospective, randomized, double-blind and placebo-controlled study has been conducted on 35 women who had to consume 25 grams/day of quinoa flakes or placebo, over a period of 4 consecutive weeks. At the beginning and at the end of the intervention, after four weeks, anthropometric assessment was performed by body weight, height and abdominal circumference; and blood was collected for the determination of glucose, total cholesterol and fractions, oxidative stress and inflammatory markers, vitamin E and enterolignans, and 24-h urine was obtained for the determination of enterolignans. The results were analyzed in two different studies which were written in the form of a scientific paper, the first one emphasizes the effect of quinoa intake on consumption on the concentrations of glucose, total cholesterol and fractions, oxidative stress markers and in the second paper investigated the effect of enterolignans on inflammatory markers in a group of postmenopausal women. Comparing the beginning and the end of the intervention, the present study showed a possible beneficial effect by quinoa intake, because significant reductions were observed in serum triglycerides, TBARS and vitamin E concentrations, and an increase in enterolignan urinary excretion in the groups that consumed quinoa and placebo. A significant reduction of total cholesterol... (Complete abstract click electronic access below) / Mestre