Oxidative stress mechanism in yeast presents an innovative pathway to understand in creating the next generation of antifungal drugs. Rgc1 and Rgc2 are paralogous proteins that regulate the Fps1 glycerol channel in hyperosmotic stress. Hyperosmotic conditions lead Hog1 MAP kinase to phosphorylate Rgc2 and cause its dissociation from Fps1, allowing the channel to close and protect the cell from damage. Rgc2 contains pleckstrin homology (PH) domains broken up by long insertions and more phosphorylation sites than targeted by Hog1 in response to hyperosmotic stress. Since none of the other MAP kinases in yeast were seen to phosphorylate Rgc2 during oxidative stress, it is thought that Rgc2 may bind to other proteins. In this study, the sensitivity of a strain deleted for both RGC1 and RGC2 was compared to strains with single deletions in either gene in response to oxidative stress. Having deletions in both RGC1 and RGC2 caused increased sensitivity to hydrogen peroxide whereas strains with deletions in either gene seemed unaffected, correlating with the fact that Rgc1 and Rgc2 are paralogous proteins, able to recover each other's functions. A second analysis compared mutated Fps1 (fps1∆-FKSV) and a strain with deletions for both RGC1 and RGC2 (rgc1/2∆). The fps1∆-FKSV strain has four amino acid substitutions in the C-terminal region where Rgc2 binds to Fps1. While both strains grew less than wild-type in hydrogen peroxide, the rgc1/2∆ strain was more sensitive suggesting that Rgc1/2 has an additional role in oxidative stress. To identify the oxidative stress function of Rgc1/2, a genomic overexpression library was transformed into the rgc1/2∆ strain and used for a suppressor screen in the presence of hydrogen peroxide. Although the screen revealed a manageable amount of 49 candidates, only four produced sequences that spanned a protein-encoding region. The candidate plasmids were transformed back into the rgc1/2∆ strain for preparation of a sensitivity assay which showed that the colonies did not survive any better than the starting rgc1/2∆ strain. Without a plausible plasmid candidate, we decided to look into the effect of YAP1 on the rgc1/2∆ strain. Yap1 is a transcription factor known to activate many genes in oxidative stress. Two forms of YAP1 were transformed into rgc1/2∆: wild-type YAP1 and YAP1-A627E which contains a mutation in the nuclear export signal. Compared to the controls, YAP1-A627E allowed the rgc1/2∆ strain to grow at 1.5mM H2O2 while wild-type YAP1 did not. This result showed that a constitutively nuclear Yap1 can overcome deletions in RGC1 and RGC2. It also suggested that an increased activity in the nucleus was important in hydrogen peroxide resistance and another suppressor screen of rgc1/2∆ was performed looking for spontaneous mutations in the genomic DNA. The screened colonies were tested for their survival on hydrogen peroxide but their resistance appeared to be transient. We have shown Rgc1 and Rgc2 to be important cellular components in oxidative stress in addition to hyperosmotic stress. Further research on Rgc1/2 would provide invaluable knowledge on oxidative stress protection in yeast and a better foundation on which to build antifungal drugs.

BACKGROUND: In recent years, studies have increasingly pointed to a number of different mechanisms that potentially form the foundation for the neurodegenerative pathology seen in Post-Traumatic Stress Disorder (PTSD). One such mechanism is neural damage due to oxidative stress. This study attempted to identify significantly altered expression levels of particular genes of interest between PTSD and control groups, as well as between PTSD samples and samples exhibiting commonly seen PTSD comorbidities, major depressive disorder (MDD), and depressive disorder not otherwise specified (DepNOS). The genes of interest being pursued in the study encompass the production of reactive oxygen species, such as inflammatory response mechanisms, the processes that control the removal of reactive oxygen species (ROS), and genes that are activated in response to oxidative stress. Other genes of interest involve factors important in the structural integrity of the prefrontal cortex, such as junction proteins, the blood-brain barrier, such as aquaporins, and neuronal integrity. These genes were included due to the evidence of structural degeneration in PTSD patients. A total of 54 genes were tested in all four groups. OBJECTIVES: To identify and determine genetic differences amongst individuals with PTSD in comparison to non-PTSD sufferers, and sufferers of common PTSD comorbidities. METHODS: The expression levels of the genes of interest were measured using quantitative polymerase chain reaction (qPCR) techniques. RNA is extracted and collected from tissues samples of deceased military PTSD patients from the prefrontal cortex. The prefrontal cortex derived RNA is used as the experimental samples, due to the prevalence of the pathology of PTSD in this region. Complimentary DNA (cDNA) is reverse transcribed from the collected RNA, and then products of genes of interest are amplified during the qPCR reaction using specifically designed primers. The expression level of the genes of interest were then compared to the ubiquitously expressed gene 18s for normalization calculations. Genetic expression levels in the PTSD, MDD, and DepNOS cohorts were then normalized to the expression of non-PTSD controls. RESULTS: Of the 54 genes of interest analyzed, two genes, NQO1 and IL-6, exhibited significantly decreased and increased levels of expression in comparison to the control group, respectively (p < 0.05). Alongside this, NQO1 showed significantly decreased expression in comparison to the DepNOS cohort, while IL-6 exhibited significantly increased expression in comparison to the MDD cohort (p < 0.05). CONCLUSION: Two genes involved with the production and elimination of reactive oxygen species were identified with having significantly altered levels of expression. NQO1, which facilitates the removal of ROS was shown to have significantly lower expression when compared to the control group, indicating an inhibited ability to remove ROS readily. Furthermore, IL-6, a proinflammatory cytokine and a promotor of ROS production, exhibited significantly increased expression, indicating a potential increase in ROS formation. Together these results indicate a potential mechanism for the production and accumulation of ROS in patients with PTSD, leading to the observed neurodegeneration. / 2018-07-11T00:00:00Z

Made available in DSpace on 2015-01-26T13:21:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-06-30Bitstream added on 2015-01-26T13:30:47Z : No. of bitstreams: 1 000797265_20160630.pdf: 140781 bytes, checksum: 4b566923c018030910c299869b78c0d1 (MD5) Bitstreams deleted on 2016-07-01T13:02:18Z: 000797265_20160630.pdf,. Added 1 bitstream(s) on 2016-07-01T13:03:16Z : No. of bitstreams: 1 000797265.pdf: 823819 bytes, checksum: 82bdb4c30be8ca9c7bb831e2a43e8816 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O estresse oxidativo e a inflamação na obesidade estão associados ao desenvolvimento de doenças crônicas, tais como o diabetes mellitus e as doenças cardiovasculares. A ingestão de dietas com alto teor de gorduras saturadas e açúcar, mas deficientes em compostos antioxidantes, contribui para o acúmulo de tecido adiposo e podem levar ao aumento de marcadores inflamatórios no sangue e tecidos. Os flavonoides cítricos possuem propriedades biológicas capazes de atenuar o estresse oxidativo e a inflamação, protegendo contra as desordens metabólicas decorrentes da obesidade e excesso de tecido adiposo. Neste trabalho foi avaliado o efeito da hesperidina, eriocitrina e eriodictiol sobre a inflamação, o estresse oxidativo e alterações no soro, fígado, coração e baço de camundongos induzidos à obesidade com dieta hiperlipídica, contendo 45% de calorias derivadas de lipídios, por quatro semanas. A hesperidina, eriocitrina e eriodictiol inibiram eficientemente o aumento dos níveis séricos de IL-6, MCP-1, proteína C-reativa, e de TBARS no fígado causado pelo consumo da dieta hiperlipídica e excesso de gordura visceral, impedindo o aumento da massa do baço e aumentando a capacidade antioxidante total no soro. A eriocitrina e eriodictiol reduziram também os níveis de TBARS no soro, enquanto o acúmulo de gordura e danos no fígado foram reduzidos pela hesperidina e eriocitrina, e a massa do coração pela hesperidina e eriodictiol. Esses resultados mostram que a hesperidina, eriocitrina e eriodictiol protegem contra a inflamação e estresse oxidativo causados pelo consumo de dieta hiperlipídica e acúmulo de gordura visceral, como indicado pela diminuição dos marcadores inflamatórios, da peroxidação lipídica, esteatose e danos hepáticos, e da massa do baço e coração, sendo bons candidatos para o tratamento das alterações primárias da obesidade, nas quais eles poderiam ajudar a prevenir o desenvolvimento de ... / Oxidative stress and inflammation in obesity are associated with the development of chronic diseases such as diabetes mellitus and cardiovascular diseases. The ingestion of diets rich in saturated fatty acids and sugar, but deficient in antioxidants, contributes to adipose tissue accumulation and may lead to increased inflammatory markers in the blood and tissues. Citrus flavonoids have biological properties capable of attenuating oxidative stress and inflammation, protecting against metabolic disorders resulting from obesity and adipose tissue excess. In the present work we assessed the effect of hesperidin, eriocitrin and eriodictyol over inflammation, oxidative stress and the changes resulting from these process in the blood serum, liver, heart and spleen of mice fed a high-fat diet, which contained 45% of calories from fat, for a period of four weeks. Hesperidin, eriocitrin and eriodictyol supplementation efficiently inhibited the increase of serum IL-6, MCP-1 and C-reactive protein, and also the TBARS levels of the liver, caused by high-fat diet ingestion and excessive visceral fat, thus preventing the increase in spleen weight and increasing serum total antioxidant capacity. Eriocitrin and eriodictyol also reduced TBARS levels in the blood serum, while liver fat accumulation and damage were reduced by hesperidin and eriocitrin, and heart weight by hesperidin and eriodictyol. These results show that hesperidin, eriocitrin and eriodictiol have protective effect against inflammation and oxidative stress caused by high-fat diet feeding and visceral obesity, as indicated by reduced liver damage and fat accumulation, and reduced heart and spleen weight, making them good candidates for use in such conditions, in which they could possibly help to prevent cardiovascular diseases ...

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Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-05-09Bitstream added on 2014-06-13T19:13:28Z : No. of bitstreams: 1 urbaczek_ac_me_arafcf.pdf: 941529 bytes, checksum: 018e3c8e75f3ede5618f06630714815e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Universidade Estadual Paulista (UNESP) / Os receptores para a porção Fc das IgG (FcgR) estão amplamente expressos nas células do sistema imune e podem estimular uma variedade de respostas efetoras. Três classes de FcgR são descritas nos humanos: FcgRI, FcgRII e FcgRIII. O neutrófilo expressa constitutivamente as isoformas FcgRIIa (CD32) e FcgRIIIb (CD16), as quais apresentam um polimorfismo funcional decorrente do polimorfismo alélico. No FcgRIIa, a substituição da histidina (H) pela arginina (R) na posição 131 resulta nas variantes polimórficas FcgRIIa- R131 e FcgRIIa-H131, que diferem quanto à capacidade de ligação à IgG2 humana. Quanto ao FcgRIIIb (CD16), o polimorfismo genético é responsável pela expressão dos antígenos de neutrófilo (NA)1, NA2 e SH e resulta em um maior número de sítios de glicosilação em NA2. O FcgRIIIb é responsável pela aproximação dos ligantes na membrana para o FcgRIIa e também interage com o receptor para complemento tipo 3 (CR3) na superfície celular. A cooperação entre os FcgRIIa/IIIb com o CR3 promove a estimulação máxima das respostas do neutrófilo, dentre elas o burst oxidativo. Uma vez que a interação FcgRIIIb/CR3 ocorre via sítio de ligação lectina-sacarídeo, o objetivo deste estudo foi avaliar se o polimorfismo alélico do FcgRIIIb poderia afetar a cooperação entre os FcgR e os CR em mediar o burst oxidativo dos neutrófilos. As freqüências dos alelos H/R-131 e NA1/NA2/SH foram analisadas por genotipagem com oligonucleotídeos alelo-específicos e reação em cadeia da polimerase e a densidade de expressão dos receptores (FcgRIIa, FcgRIIIb, CR1 e CR3) foi determinada por citometria de fluxo. A distribuição dos genótipos para o FcgRIIIb (n=169) foi NA1/NA2 (52,1%), NA2 (27,8%) e NA1 (20,1%). Dentre 174 indivíduos, apenas 6,3% apresentaram o gene SH. Quanto aos genótipos para o FcgRIIa (n=143), a distribuição... / Receptors for immunoglobulin G (FcgR) are known to be expressed on many cells of the immune system and they can trigger a variety of biological responses. Human FcgR belong to the Ig superfamily and three classes of these receptors have been recognized: FcgRI, FcgRII and FcgRIIl, with different affinities and specificities for IgG subclasses. Neutrophils express the FcgRIIa (CD32) and FcgRIIlb (CD16) isoforms, which display a functional polymorphism due to biallelic polymorphisms. In the case of FcgRIIa, an arginine (FcgRIIa-R131) or histidine (FcgRIIa-H131) at amino acid position 131 determines receptor affinity for IgG2, FcgRIIa-H131 being the isoform with highest affinity. On neutrophils, the FcgRIIIb bears the neutrophil antigen (NA) polymorphism, NA1, NA2 and SH, NA2 being the more glycosylated isoform. Cooperation of FcgRIIIb with FcgRIIa and CR3 (complement receptor type 3) is necessary for efficient neutrophil responses, including the oxidative burst. Since the FcgRIIIb/CR3 cooperation occurs via lectin-sacharide-like interaction, the aim of this study was to evaluate whether the allelic polymorphism, NA1 and NA2, could influence the cooperation of FcgRIIIb with CR3 in mediating the oxidative burst of neutrophils. FcgRIIa and FcgRIIIb genotyping analysis were performed by polymerase chain reaction with allelespecific primers and surface expressions of FcgRIIa, FcgRIIIb, CR1 and CR3 on neutrophils were determined by flow cytometry. The FcgRIIIb genotype distribution (n=169) was NA1/NA2 (52.1%), NA2 (27.8%) and NA1 (20.1%). SH gene was found in 11 (6.3%) volunteers from 174 subjects. With respect to the FcgRIIa genotype (n=143), the distribution observed was R131 (41.2%), H/R131 (38.5%) and H (20.3%). Neutrophils were stimulated with immune complexes (IC)-IgG opsonized or not with complement and the oxidative burst... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-09Bitstream added on 2014-06-13T20:41:36Z : No. of bitstreams: 1 silva_aa_dr_botfmvz.pdf: 1478521 bytes, checksum: 3590a41144246c2ed3a4619905b51919 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Nas espécies domésticas as pneumonias cursam com intensa resposta inflamatória e acúmulo de células fagocíticas nos pulmões, levando a danos expressivos das estruturas do trato respiratório e à função pulmonar devido ao estresse oxidativo decorrente da liberação de grandes quantidades de Espécies Reativas do Oxigênio (ERO) durante a explosão respiratória. O objetivo deste estudo foi analisar o status oxidativo, a resposta inflamatória e a gasometria arterial, de ovinos sadios (n=20) e com diagnóstico clínico de pneumonia (n=20). Inicialmente os animais foram submetidos ao exame clínico e divididos em dois grupos: I) G1/controle, composto pelos animais clinicamente sadios e II) G2, composto pelos animais portadores de pneumonia. O status oxidativo foi avaliado por determinação indireta da atividade enzimática da Superóxido Dismutase (SOD) e Glutationa Peroxidase (GSH-Px) e das concentrações de Glutationa total (GSH-t) e Substâncias Reativas ao Ácido Tiobarbitúrico (TBARS) no sangue periférico por método colorimétrico. A resposta inflamatória foi avaliada pelo hemograma e proteína total e fibrinogênio plasmáticos e a função pulmonar pela determinação das variáveis hemogasométricas Pressão Arterial de Oxigênio (PaO2), Pressão Arterial de Gás Carbônico (PaCO2), Hidrogeniônico (pH), Saturação de Oxigênio (SO2), Bicarbonato (HCO3¯), Dióxido de Carbono Total (TCO2) e Excesso de Bases (EB), avaliados em sangue arterial. O leucograma revelou leucocitose com neutrofilia, eosinofilia, monocitose e linfopenia nos animais doentes (p<0,05). Com relação aos parâmetros bioquímicos, os ovinos portadores de pneumonia apresentaram aumento significativo (p>0,05) da concentração de fibrinogênio e proteína plasmática total. Os animais portadores de pneumonia apresentaram diminuição estatisticamente... / In domestic species, pneumonia is accompanied by intense inflammatory response and accumulation of phagocytic cells in the lungs, causing structural damage of the respiratory tract due to oxidative stress resulting from the release of large amounts of Reactive Oxygen Species (ROS) during the respiratory burst. The aim of this study was to analyze the oxidative status, inflammatory response and arterial blood gases values in healthy sheep (n=20) and animals with a clinically diagnosed pneumonia (n = 20). After physical examination the animals were divided into two groups: i) G1/control, composed of clinically healthy animals and ii) G2, composed of animals with pneumonia. The oxidative status was assessed by indirect determinations of enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentrations of total glutathione (GSH-t) and thiobarbituric acid reactive substances (TBARS) in peripheral blood by a colorimetric method. The inflammatory response was evaluated by complete blood count and total protein and plasma fibrinogen. The lung function was evaluated by determinations of blood gas parameters in arterial blood: Oxygen Pressure (PaO2) Pressure of Carbon Dioxide (PaCO2), Pressure Hydrogen (pH), Oxygen Saturation (SO2), Bicarbonate (HCO3¯), Total Carbon Dioxide (TCO2) and Base Excess (EB). The leucogram results showed Leukocytosis with neutrophilia, eosinophilia, monocytosis and lymphopenia in sick animals (p<0,05). With regard to biochemical parameters, sheep with pneumonia showed a significant increase (p<0,05) of fibrinogen and total plasma protein concentrations. The animals from group G2 had a statistically significant reduction (p<0,05) in SOD and GSH-Px enzymatic activity and GSH-t concentration, while TBARS concentration was significantly higher (p<0,05). Arterial blood... (Complete abstract click electronic access below)

Diet-derived polyphenols are believed to have health benefits on account of their antioxidant properties. Cardiovascular health is considered to be a suitable target for antioxidant therapy because oxidative stress is implicit in atherogenesis – the disease process that underpins heart attacks, ischaemic strokes and peripheral vascular disease. Numerous in vitro, in vivo and clinical studies indicate that polyphenols are protective in cardiovascular disease, but their mechanism of action still remains ambiguous. This thesis describes a wide range of studies to characterise the activity and stability of a key polyphenol, delphinidin, found in widely consumed berries, and ultimately to test the hypothesis that delphinidin, at physiologically relevant concentrations (~1 µM), protects cultured human umbilical vein endothelial cells (HUVECs) against oxidative damage via a mechanism that is independent of direct antioxidant activity. Delphinidin aglycone was found to be unstable in tissue culture medium, in which it decomposed rapidly to simple phenolic compounds, including gallic acid. Electron paramagnetic resonance spectroscopy indicated that, if anything, both delphinidin and gallic acid were pro-oxidant rather than antioxidant. Moreover, high concentrations of both delphinidin and gallic acid induced rapid morphological changes in HUVECs, most notably in the formation of vacuoles or vesicles. Treatment of HUVECs with a range of concentrations (1 nM - 100 µM) of delphinidin and gallic acid showed that high (100 µM) concentrations of both were cytotoxic. However, both agents were found to have a protective effect in cells exposed to oxidative stress when present at concentrations of ~1 µM – too low to be due to direct antioxidant activity. Deeper examination of cells treated with delphinidin and gallic acid indicated that the protective effect was perhaps partially mediated by changes in expression of the intracellular antioxidant, glutathione. Taken together, the results in this thesis suggest that metabolic products of delphinidin might be responsible for the antioxidant effects seen on account of initiating cellular defence responses.

Made available in DSpace on 2014-06-11T19:27:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-29Bitstream added on 2014-06-13T18:32:13Z : No. of bitstreams: 1 teixeira_o_me_botfm.pdf: 201581 bytes, checksum: 11c447de3ec6c3b94411cfd1f2894923 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O sedentarismo é considerado o maior problema de saúde pública do século XXI. A baixa capacidade cardiorrespiratória (VO2máx) está associada aos altos índices de mortalidade por todas as causas e ao desenvolvimento de doenças crônicas nãotransmissíveis (DCNT). O exercício físico regular é tido como conduta terapêutica e preventiva contra o aparecimento e desenvolvimento desses fatores de risco para doença cardivascular (DCV). Na presença de 3 ou mais desses fatores de risco (hiperglicemia, obesidade do tipo central, hipertensão arterial e dislipidemia), é diagnosticado a síndrome metabólica (SM). Os objetivos do presente estudo foram avaliar o VO2máx de acordo com o número de componentes da SM e identificar os componentes da SM preditores do baixo VO2máx. Foram avaliados 551 indivíduos de ambos os sexos com faixa etária superior a 35 anos. A avaliação clínica consistiu da medição da pressão arterial de repouso e da anamnese clínica. A composição corporal foi avaliada por meio da impedância bioelétrica afim de determinar o percentual de gordura e o índice de massa corporal. O VO2máx foi obtido por teste de caminhada em esteira rolante utilizando o protocolo de Balke modificado até a exaustão voluntária do indivíduo. Foram coletadas amostras sanguíneas para dosagens de indicadores bioquímicos do estresse inflamatório/oxidativo e das variáveis plasmáticas para diagnóstico da SM. O critério diagnóstico da SM utilizado foi o da National Cholesterol Education Program Adult’s Treatment Panel III (NCEPIII). O VO2máx (mL.kg-1.min-1)foi menor na mulheres (30,9 x 37,8) e nos indivíduos com idade superior a 60 anos (33,9 x 28,9). Foi decrescente com o aumento do número de componentes alterados e o triglicerídio plasmático foi o principal componente preditor do baixo VO2máx. A capacidade cardiorrespiratória diminui com o aumento do número... / Sedentary lifestyle is considered the biggest public health of the 21st century. Low cardiorespiratory fitness (VO2max) is associated to mortality and chronic diseases. Regular physical activity has been taken as a therapeutic and preventive conduct against cardiovascular disease risk factors. The existence of at least three risk factors (hyperglicemia, central obesity, hypertension, hypertrigliceridemia, low HDL-C) defines metabolic syndrome (MS). The purposes oh the present study was to associated the VO2max with the number of MS components and identify low VO2max predictors. 551 subjects older than 35 years old of both sexes were evaluated. Blood pressure was measured from patients in seated position, and patients medicaly eligible performed treadmill stress test according to a modified Balke protocol until voluntary exhaustion. Body composition was evaluated with impedance bioeletrical. Participants were asked to fast for at least 12 h for blood collection in accordance to CeMENutri protocol and processed at central laboratory. Metabolic syndrome was defined by National Cholesterol Education Program based on the presence of at least three altered components. Women and individuals older than sixty years old had lower VO2max (mL.kg- 1.min-1) (30,9 and 28,9) than men and younger subjects (37,8 and 33,9). The VO2max is inversely associated with number of MS components and after adjusts for age, sex, and obesity, hypertriglyceridemia was major low VO2max predictor. Cardiorespiratory fitness is diminished with increase MS components and plasma trygliceridios was major predictor

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2010 / Consumption of sucrose with a meal containing oxidised and oxidisable lipids cause an increase in oxidative stress which is referred to as postprandial oxidative stress. The modulating effect on postprandial oxidative stress by an antioxidant-rich beverage, fermented rooibos (Aspalathus linearis) was compared to that of a commercial soft drink (soda). Both study beverages contained sucrose and were consumed with a standardised fat meal. The study consisted of two parts, a pilot study (Phase One) where participants consumed either a standardised fat meal with water (control group n = 5) or a standardised fat meal with a sucrose-containing commercial soda (treatment group n = 8) using a parallel design, and the experimental study (Phase Two) where participants (n = 14) consumed the standardised fat meal with the commercial soda (control group) or the rooibos beverage (treatment group) using a crossover design. Specific analytical techniques and methods for determination of plasma glucose, serum insulin, lipid profile, an inflammatory indicator (high sensitive C-reactive protein), plasma antioxidant capacity, whole blood redox status and plasma lipid oxidation biomarkers were used. Results from the pilot study indicated significantly (P<0.05) higher postprandial levels of glucose in the control group at 4 hr and 6hr postprandially. The inflammatory biomarker and triglyceride levels were significantly (P<0.05) elevated in both groups when compared to their respective baselines. Results also showed the total antioxidant capacity and total glutathione levels in the plasma of both groups to be significantly (P<0.05) lowered when compared to the baseline values. The level of lipid oxidation biomarkers in the plasma was significantly (P<0.05) higher at 2 hr, 4 hr and 6 hr post time intervals for thiobarbituric acid reactive substances and 4 hr post time interval for conjugated dienes in the participants consuming the standardised fat meal with soda when compared to the baseline value, while this was reflected only at 2 hr post time interval for thiobarbituric acid reactive substances, with the conjugated dienes levels being significantly (P<0.05) lowered at 6 hr post time interval in the control group. No differences were shown on inter group level for the pilot study. On inter group level, results from Phase Two showed significant (P<0.05) lower levels of plasma glucose at 6 hr post time interval in the treatment group when compared to the control group, with insulin levels being significantly (P<0.05) higher in the control group at 4 hr post time interval.

Orientador: Thais Borges Cesar / Banca: Amanda Martins Baviera / Banca: Luis Carlos Spolidorio / Resumo: O estresse oxidativo e a inflamação na obesidade estão associados ao desenvolvimento de doenças crônicas, tais como o diabetes mellitus e as doenças cardiovasculares. A ingestão de dietas com alto teor de gorduras saturadas e açúcar, mas deficientes em compostos antioxidantes, contribui para o acúmulo de tecido adiposo e podem levar ao aumento de marcadores inflamatórios no sangue e tecidos. Os flavonoides cítricos possuem propriedades biológicas capazes de atenuar o estresse oxidativo e a inflamação, protegendo contra as desordens metabólicas decorrentes da obesidade e excesso de tecido adiposo. Neste trabalho foi avaliado o efeito da hesperidina, eriocitrina e eriodictiol sobre a inflamação, o estresse oxidativo e alterações no soro, fígado, coração e baço de camundongos induzidos à obesidade com dieta hiperlipídica, contendo 45% de calorias derivadas de lipídios, por quatro semanas. A hesperidina, eriocitrina e eriodictiol inibiram eficientemente o aumento dos níveis séricos de IL-6, MCP-1, proteína C-reativa, e de TBARS no fígado causado pelo consumo da dieta hiperlipídica e excesso de gordura visceral, impedindo o aumento da massa do baço e aumentando a capacidade antioxidante total no soro. A eriocitrina e eriodictiol reduziram também os níveis de TBARS no soro, enquanto o acúmulo de gordura e danos no fígado foram reduzidos pela hesperidina e eriocitrina, e a massa do coração pela hesperidina e eriodictiol. Esses resultados mostram que a hesperidina, eriocitrina e eriodictiol protegem contra a inflamação e estresse oxidativo causados pelo consumo de dieta hiperlipídica e acúmulo de gordura visceral, como indicado pela diminuição dos marcadores inflamatórios, da peroxidação lipídica, esteatose e danos hepáticos, e da massa do baço e coração, sendo bons candidatos para o tratamento das alterações primárias da obesidade, nas quais eles poderiam ajudar a prevenir o desenvolvimento de ... / Abstract: Oxidative stress and inflammation in obesity are associated with the development of chronic diseases such as diabetes mellitus and cardiovascular diseases. The ingestion of diets rich in saturated fatty acids and sugar, but deficient in antioxidants, contributes to adipose tissue accumulation and may lead to increased inflammatory markers in the blood and tissues. Citrus flavonoids have biological properties capable of attenuating oxidative stress and inflammation, protecting against metabolic disorders resulting from obesity and adipose tissue excess. In the present work we assessed the effect of hesperidin, eriocitrin and eriodictyol over inflammation, oxidative stress and the changes resulting from these process in the blood serum, liver, heart and spleen of mice fed a high-fat diet, which contained 45% of calories from fat, for a period of four weeks. Hesperidin, eriocitrin and eriodictyol supplementation efficiently inhibited the increase of serum IL-6, MCP-1 and C-reactive protein, and also the TBARS levels of the liver, caused by high-fat diet ingestion and excessive visceral fat, thus preventing the increase in spleen weight and increasing serum total antioxidant capacity. Eriocitrin and eriodictyol also reduced TBARS levels in the blood serum, while liver fat accumulation and damage were reduced by hesperidin and eriocitrin, and heart weight by hesperidin and eriodictyol. These results show that hesperidin, eriocitrin and eriodictiol have protective effect against inflammation and oxidative stress caused by high-fat diet feeding and visceral obesity, as indicated by reduced liver damage and fat accumulation, and reduced heart and spleen weight, making them good candidates for use in such conditions, in which they could possibly help to prevent cardiovascular diseases ... / Mestre