This study investigated the influence of dietary antioxidants and quality of oil on the oxidative and enzymatic properties of chicken broiler meat stored in an oxygen-enriched package (HiOx: 80% O2/20% CO2) in comparison with air-permeable polyvinylchloride (PVC) or skin (SK) packaging systems during retail display 2–4 °C for up to 14, 7, and 21 d, respectively. Broilers were fed a diet either with a low-oxidized oil (peroxide vale POV 23 meq O2/kg) or with a high-oxidized oil (POV 121 meq O2/kg), supplemented with an antioxidant pack (200 ppm EconomasE and organic minerals Se, Zn, Cu, Mn, and Fe as in Bioplex) in substitution for vitamin E and inorganic minerals for 42 d. In all packaging systems, lipid oxidation and protein oxidation were inhibited by up to 65% with an antioxidant-supplemented diet when compared to diets without antioxidant supplements. Antioxidant enzyme activities were significantly higher (P < 0.05) in the antioxidant-supplemented diets compared with control diets, regardless of oil quality. Meat samples from the antioxidant-supplemented group, irrespective of oil quality, has less purge and cooking loss compared to control diets. In all packaging systems, meat shear force was higher (P < 0.05) for broilers fed high-oxidized diets than the low-oxidized groups. Comparison between muscle types (breast as white vs. thigh as red) showed a similar trend in muscle susceptibility to oxidized oil in the diet but greater protection of antioxidant supplements for thigh meat in both physiochemical and textural properties. Dietary regimen influenced protein expression in broiler breast meat. Three protein spots from 2-dimensional gel electrophoresis, identified by mass spectrometry as glyceraldehyde 3-phosphate dehydrogenase, creatine kinase, and heat shock protein beta-1 were over-abundant in muscle from low-oxidized diets. The differential proteomes that suggested down regulation of the genes encoding antioxidative proteins upon feeding oxidized oil may be implicated in the broiler meat quality deterioration during storage. In summary, feeding diets with poor oil quality increased the vulnerability of lipids and proteins to oxidation in broiler breast and thigh meat during refrigerated and / or frozen storage in various packaging conditions, yet these effects were alleviated upon dietary supplementation with antioxidants.

Orientador: Wilson Nadruz Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T13:58:57Z (GMT). No. of bitstreams: 1 Paim_LaydeRosane_M.pdf: 776318 bytes, checksum: f8e1046411d4b45041c7d37ca207a89e (MD5) Previous issue date: 2014 / Resumo: Estudos prévios mostram que indivíduos com lesão crônica na medula espinhal (LM) apresentam maior risco cardiovascular em comparação com indivíduos fisicamente normais. O presente estudo investigou a relação entre os níveis plasmáticos da lipoproteína de baixa densidade oxidada (LDLox), as metaloproteinases de matriz (MMP) e seus inibidores teciduais (TIMPs) e o remodelamento vascular em pacientes com LM, e o papel da atividade física nesta relação. Foram estudados 42 homens com LM (? 2 anos), [18 sedentários (S-LM) e 24 fisicamente ativos (A-LM)] e 16 homens fisicamente saudáveis por meio de análise clínica, antropométrica, laboratorial e de espessura íntima-média da carótida (EIM). Todos os participantes estudados eram normotensos, não diabéticos, não fumantes e normolipêmicos. As concentrações plasmáticas de LDLox, MMP-2, MMP-8, MMP-9, TIMP-1 e TIMP-2 foram determinados por ensaio imunoenzimático (ELISA). Os resultados mostraram que a EIM da carótida, razão EIM/diâmetro e as concentrações de LDLox dos A-LM e dos indivíduos fisicamente normais não foram diferentes estatisticamente. Por outro lado, indivíduos com S-LM apresentaram maior EIM, razão EIM/diâmetro e concentrações aumentados de LDLox em comparação com A-LM (p<0,01, p<0,001 e p=0,01, respectivamente) e indivíduos controles (p<0,001 para todos). Os resultados da análise de correlação bivariada, incluindo todos os indivíduos com LM, demonstrou que o EIM de carótida e a razão EIM/diâmetro se correlacionaram apenas com LDLox, MMP-8 e com a relação MMP-8/TIMP-1. Além disso, a análise de regressão ajustada para a presença ou não de atividade física e idade mostrou que a LDLox foi associada à EIM carotídea e com a relação EIM/diâmetro, enquanto que MMP-8 foi associado com o índice EIM/diâmetro em indivíduos com LM. Em conclusão, as concentrações plasmáticas de LDLox e MMP-8 estão associados com aterosclerose carotídea e há interação entre a inatividade física, aterosclerose e LDLox em indivíduos com LM / Abstract: Previous reports have indicated that subjects with chronic spinal cord injury (SCI) exhibit increased cardiovascular risk compared to able-bodied individuals. This study investigated the relationship between plasmatic oxidized low-density lipoprotein (OxLDL), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) levels and vascular remodeling in SCI subjects and the role of physical activity in this regard. We studied 42 men with chronic (?2 years) SCI [18 sedentary (S-SCI) and 24 physically active (PA-SCI)] and 16 able-bodied men by clinical, anthropometric, laboratory, and carotid intima-media thickness (IMT) analysis. All enrolled subjects were normotensive, non-diabetics, non-smokers and normolipemic. Plasmatic OxLDL, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay. The results showed that carotid IMT, IMT/diameter ratio and OxLDL levels of PA-SCI and able-bodied subjects were statistically similar. Conversely, S-SCI subjects exhibited higher IMT, IMT/diameter ratio and OxLDL levels compared to PA-SCI (p<0.01, p<0.001 and p=0.01, respectively) and able-bodied (p<0.001 for all) individuals. Results of bivariate correlation analysis including all injured subjects showed that carotid IMT and IMT/diameter ratio only correlated with OxLDL, MMP-8 and MMP-8/TIMP-1 ratio. Further stepwise regression analysis adjusted for the presence or not of physical activity and age showed that OxLDL was associated with carotid IMT and IMT/diameter ratio, while MMP-8 was associated with IMT/diameter ratio in SCI individuals. In conclusion, plasmatic OxLDL and MMP-8 levels are associated with carotid atherosclerosis and there is an interaction among physical inactivity, atherosclerosis and OxLDL in SCI individuals / Mestrado / Clinica Medica / Mestra em Clínica Médica

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Epidemiological studies have suggested that intake of fruits and vegetables act in the prevention of several diseases such as cancer and cardiovascular diseases. This can be explained by these bioactive compounds are present in their food nutritional matrix that may have different biological activities, including antioxidant, antitumor, genoprotective and in preventing the oxidation of LDL. However, much of the fruit remains to be studied. This is the case of Solanum sessiliflorum popularly known as mana-cubiu or cubíu fruit coming from the Amazon region of Brazil, considered the "Amazonian apple". This fruit is popularly used as a medicine to control the itching of the skin and reducing cholesterol levels, glucose and uric acid in the blood. Once S. sessiliflorum studies are still incomplete, the aim of this study was to chemically characterize the extract and perform tests to determine their prospecting potential antioxidant, antitumoral and effect in vitro on preventing the oxidation of LDL. For this, the study was conducted in two stages, the first stage was prepared hydroalcoholic extract of the peel and seed and pulp. After preparation of the extract, the chemical characterization was conducted by the same determination of total bioactive compounds (flavonoids, tannins and polyphenols), then the extract was chemically characterized by high performance liquid chromatography (HPLC). In the second step, we evaluated the antioxidant potential and in citoprotetor in and in PBMC (Peripheral Blood Mononuclear Cells) and human plasma exposed to hydrogen peroxide (H2O2). We also evaluated the antitumor activity in lines of breast (MCF7) and colorectal (HT29) cancer cell cancer, assessing cell proliferation and viability. After this, the effect has been evalueted on the oxidation of LDL (isolated from healthy individuals). The results obtained indicate that the extract of Solanum sessiliflorum presents in its composition total bioactive compounds such as flavonoids, tannins and polyphenols. These results corroborate the analysis performed by HPLC which indicated that the extracts present in its composition gallic acid, caffeic acid, quercetin, rutin, β carotene and catechin (the latter except in the pulp and seed extract). When examined the in vitro antioxidant effect was observed that extracts at different concentrations did not show any pro-oxidant potential. However extract the pulp and the seeds had antioxidant and cytoprotective activity. It was also observed that the extract of the pulp and the seeds had antigenotoxic and specific antitumor activity for colorectal cancer cells (in vitro tests performed with strain HT29 cells), and no antitumor activity was observed for breast cancer cells (MCF7), instead of the expected high concentrations in the extract increased the viability and proliferation. Another important finding was that both extracts, seeds and pulp and peel showed potential for inhibiting oxidation of LDL. In synthesis, the in vitro results obtained data indicate that S. sessiliflorum has antioxidant, antitumor and citoprotetor activity and present potential to inhibit the oxidation of LDL. These results should be proof of the presence of bioactive compounds in its composition as flavonoids, polyphenols and catechins. In literature there are several studies that report that eating foods rich in these types of compounds are related to the prevention of several chronic diseases, such as cancer and cardiovascular diseases. / Estudos epidemiológicos têm sugerido que a ingestão de frutas e verduras atuam na prevenção de diversas patologias, tais como o câncer e doenças cardiovasculares. Isto pode ser explicado por estes alimentos apresentarem compostos bioativos na sua matriz nutricional que podem ter diversas atividades biológicas, incluindo atividade antioxidante, antitumoral, genoprotetor e na prevenção da oxidação do LDL. Entretanto, uma grande parte dos frutos ainda precisa ser estudada. Este é o caso do Solanum sessiliflorum popularmente conhecido como mana-cubiu ou cubíu fruto oriundo da região amazônica do Brasil, considerado a maçã amazônica que é popularmente utilizado como medicamento no controle do prurido da pele e na redução dos níveis de colesterol, glicose e ácido úrico no sangue. Uma vez que estudos sobre o S. sessiliflorum são ainda incipientes, o objetivo deste estudo foi caracterizar quimicamente o extrato de S. sessiliflorum e realizar ensaios de prospecção para determinar seu potencial efeito antioxidante, antitumoral e na prevenção da oxidação do colesterol LDL através de ensaios in vitro. Para isto, o estudo foi conduzido em duas etapas, na primeira etapa foram preparados dois extratos hidroalcóolicos 1) da casca e 2) da semente e polpa do S. sessiliflorum. Após preparo do extrato, foi conduzida a caracterização química do mesmo através da determinação de compostos bioativos totais (flavonoides, taninos e polifenóis), em seguida, o extrato foi caracterizado quimicamente por cromatografia líquida de alta eficiência (CLAE). Na segunda etapa, foi avaliado o potencial antioxidante e citoprotetor em plasma humano exposto ao peróxido de hidrogênio (H2O2) e também em PBMCs (Peripheral Blood Mononuclear Cells). Também foi verificada a atividade antitumoral em linhagens de célula de câncer de mama (MCF7) e de câncer de colorretal (HT29), avaliando a proliferação e a viabilidade celular. Após, foi avaliado o efeito na oxidação do LDL (isolado de indivíduos saudáveis). Os resultados obtidos indicam que o extrato de Solanum sessiliflorum apresenta em sua composição compostos bioativos totais como os flavonóides, taninos e polifenóis. Estes resultados corroboram com as análises realizadas por CLAE que indicaram que os extratos apresentam em sua composição ácido gálico, ácido caféico, quercetina, rutina, β-caroteno e catequina (este último exceto no extrato de polpa e semente). Quando analisado o efeito antioxidante in vitro foi observado que os extratos nas concentrações testadas não apresentaram potencial pró-oxidante. No entanto o extrato da polpa e da semente apresentou atividade antioxidante e citoprotetora. Também foi observado que o extrato da polpa e da semente apresentou atividade antigenotóxica e antitumoral específica para células de câncer de colorretal (teste in vitro realizado com linhagem de células HT29), e não foi observado atividade antitumoral em relação à linhagem de células de câncer de mama (MCF7), pelo contrário do esperado, em altas concentrações o extrato aumentou a viabilidade e a proliferação celular. Outro importante achado foi que ambos os extratos, semente e polpa e casca apresentaram potencial de inibição da oxidação do LDL. Em síntese, os dados obtidos nos experimentos in vitro indicam que o S. sessiliflorum apresenta atividade antioxidante, antitumoral, antigenotóxica e potencial de inibir a oxidação do LDL. Estes resultados devem-se a presença de compostos bioativos em sua composição como flavonóides, polifenóis e catequina. Na literatura há diversos estudos que relatam que a ingestão de alimentos ricos nestes tipos de compostos está relacionada à prevenção de diversas doenças crônicas, como o câncer e doenças cardiovasculares.

Abstract Atherosclerosis is a multifactorial disease with numerous genes and environmental factors affecting its intiation and progression. During the past years many candidate genes for atherosclerosis have been suggested, and it has also become evident that the immune system plays a part in atherogenesis. Early atherosclerotic changes can be effectively detected by measuring carotid artery intima-media thickness (IMT). In the present study the associations between IMT and polymorphisms of three candidate genes for atherosclerosis were studied: endothelial nitric oxide synthase (eNOS), apolipoprotein E (apoE) and paraoxonase-1 (PON1). To assess the role of immunological factors determining carotid atherosclerosis, CRP and circulating autoantibodies to oxidised LDL were studied in relation to IMT. The study population consisted of 519 hypertensive and 526 control subjects from a middle-aged population in Oulu, Finland. The results showed that the investigated polymorphisms of eNOS and PON1 genes were not associated with IMT, suggesting that these polymorphisms are not major risk factors for atherosclerosis in the general Caucasian population. A significant interaction between the apoE polymorphism and smoking in relation to IMT was observed among men, indicating that carriers of the ε4 allele may be particularly prone to the atherogenic effects of smoking. This interaction was especially clear in hypertensive subjects. CRP was strongly associated with IMT before adjusting for confounding factors. After the adjustment, this association diasppeared. The finding suggests that instead of early atherosclerosis CRP may be related to the later phases of the disease. This may partly explain the strong correlation between CRP and future cardiovascular events. IgM type of autoantibodies binding to oxidised LDL were inversely associated with IMT, and this finding remained after adjusting for previously known risk factors for atherosclerosis, implying a possible protective role for these antibodies in atherogenesis.

Předkládaná dizertační práce se zabývá vývojem technologie výroby nového typu biodegradabilních vláken na bázi oxidované kyseliny hyaluronové. V rámci práce je postupně představován vývoj jednotlivých jednotkových operací výroby, jejichž správné porozumění a schopnost jejich řízení jsou klíčové pro žádaný chod celé vícestupňové technologie. V rámci práce je představen nezbytný vývoj technologického zařízení, průběžně konstruovaného pro účely laboratorního testování a následně až po samotnou linku pro finální výrobu vláken, která byla realizována v roce 2015. V rámci dizertační práce jsou dále navrhovány možnosti dodatečné chemické úpravy vláken s ohledem na zvyšování jejich stability ve vlhkém prostředí. S ohledem na cílené aplikace vláken pro vnitřní chirurgické implantace, jsou v práci vlákna též hodnocena z hlediska jejich materiálové biokomaptibility (toxicity).

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Ingrid Salanciová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Interactions of reduced and oxidized glutathione with copper, iron and zinc Copper (Cu), iron (Fe) and zinc (Zn) are important trace elements that are necessary for proper function of the body. Excess but also the lack of these metals may lead to pathological conditions. Glutathione is the main antioxidant in the human body so it is expected to protect the organism against concequences of metal excess. Glutathione occurs in the reduced (GSH) and oxidized state as glutathione disulfide (GSSG) in the organism, both states forming an important redox system. On the other hand, glutathione can reduce these metals so that could participate in the formation of free radicals (metal based Fenton reaction). In this diploma thesis, was tested the ability of reduced and oxidized glutathione to interact with Fe, Cu and Zn in various (patho) physiological pH conditions was tested by using in vitro spectrophotometric competitive methods. Interactions include not only the chelation of Cu, Fe and Zn ions, but also their reductive activity toward Cu2+ and Fe3+ cations. Hematoxylin, bathocuproinedisulfonic acid disodium salt, ferrozine...

C-reactive protein (CRP) is secreted by hepatocytes as a pentameric molecule made up of identical monomers, circulates in the plasma as pentamers, and localizes in atherosclerotic lesions. In some cases, localized CRP was detected by using monoclonal antibodies that did not react with native pentameric CRP but were specific for isolated monomeric CRP. It has been reported that, once CRP is bound to certain ligands, the pentameric structure of CRP is altered so that it can dissociate into monomers. Accordingly, the monomeric CRP found in atherosclerotic lesions may be a stationary, ligand-bound, by-product of a ligand-binding function of CRP. CRP binds to modified forms of low-density lipoprotein (LDL). The binding of CRP to oxidized LDL requires acidic pH conditions; the binding at physiological pH is controversial. The binding of CRP to enzymatically-modified LDL occurs at physiological pH; however, the binding is enhanced at acidic pH. Using enzymatically-modified LDL, CRP has been shown to prevent the formation of enzymatically-modified LDL-loaded macrophage foam cells. CRP is neither pro-atherogenic nor atheroprotective in ApoE-/-and ApoB100/100Ldlr-/-murine models of atherosclerosis, except in one study where CRP was found to be slightly atheroprotective in ApoB100/100Ldlr-/-mice. The reasons for the ineffectiveness of human CRP in murine models of atherosclerosis are not defined. It is possible that an inflammatory environment, such as those characterized by acidic pH, is needed for efficient interaction between CRP and atherogenic LDL during the development of atherosclerosis and to observe the possible atheroprotective function of CRP in animal models.

Oxidized low-density lipoproteins (OxLDL) mediate many of the pathological events associated with atherosclerosis. Oxysterols, the major cytotoxic component of OxLDL, induce apoptosis in macrophages by a calcium flux mediated activation of cytosolic phospholipase A2 resulting in the release of arachidonic acid (AA). Inhibition of AA metabolism has been shown to protect macrophages from oxysterol-induced apoptosis. The current study explores the steps in the oxysterol-induced apoptosis signaling pathway in murine macrophages subsequent to the liberation of AA. To elucidate this mechanism, two oxysterols, 7-ketocholesterol and 25-hydroxycholesterol (25-OHC), were used to induce apoptosis in murine macrophage cell lines (P388D1, and Raw 264.7) and mouse peritoneal macrophages (MPMs). Pharmacological inhibition of eicosanoid synthesis or genetic knockout of important eicosanoid biosynthetic genes had no significant effect on the induction of apoptosis by oxysterols in macrophages. The induction of apoptosis in macrophage cell lines and MPMs by oxysterols and OxLDL was suppressed by Sandoz 58-035, an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT). Furthermore, in comparison to wild-type MPMs, ACAT-1 deficient MPMs were found to be resistant to apoptosis induced by oxysterols or OxLDL. Macrophages treated with 7KC accumulated ACAT-derived cholesteryl and 7-ketocholesteryl esters. An inhibitor of cholesterol trafficking, U18666A, specifically prevented the accumulation of cholesteryl esters, but not 7-ketocholesteryl esters nor the induction of apoptosis. An inhibitor of cPLA2 prevented the accumulation of 7-ketocholesteryl esters. This inhibition was reversed by supplementing oleic acid or AA; however, only AA supplementation restored the induction of apoptosis. These results suggest that oxysterols not only initiate the apoptosis pathway by activating cPLA2, but also participate in the downstream signaling pathway when esterified by ACAT to form arachidonyl oxysterols. We also demonstrate that macrophages lacking the cannabinoid type-2 (CB2) receptor have reduced levels of apoptosis when treated with oxysterols or OxLDL in comparison to wild-type macrophages and that a CB2 specific antagonist blocks oxysterol-induced apoptosis in macrophages suggesting that the CB2 receptor is involved in this pathway, perhaps by interacting with the arachidonyl oxysterols.

Platelet-activating factor acetylhydrolase (PAFAH) is elevated in atherosclerosis and may play a role in pathogenesis of this disease. Molecular mechanisms regulating the expression of this lipoprotein-associated PLA2 are indistinct. Mildy oxidized low density lipoprotein (oxLDL) and monocytes (the primary source of PAFAH) are co-localized in early atheromas. Monocytes are activated by oxidized phospholipids (oxPL) in the oxLDL particle. We hypothesized that oxPL-activated monocytes are the source of increased levels of PAFAH in atherosclerosis. We found that PAFAH expression is significantly induced by OxPAPC and in particular long-chain fractions of oxPAPC in monocytes and cytokine-differentiated DC, but not cytokine-differentiated MO. Furthermore, spontaneously differentiated MO and DC from monocytes of non-periodontitis and aggressive periodontitis subjects, oxPAPC induced PAFAH in DC alone. 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphocholine (PEIPC) is a particularly bioactive component of long-chain oxPAPC fractions that binds the prostaglandin receptor subtypes DP1 and EP2. We revealed using selective agonists and antagonists of these receptors that DP1 and EP2 are required for the induction of PAFAH expression. OxPAPC stimulates IL-6 release from monocytes and this cytokine is required for oxPAPC-induced PAFAH expression. We next tested the hypothesis that oxPAPC did not induce PAFAH in MO because a key component of the signaling machinery was lacking. Flow cytometric and immunoblot analyses demonstrated that MO express very low levels of IL-6 receptor in comparison to DC and monocytes. Based on these observations, we propose that long-chain oxPL induce PAFAH expression by binding DP1 and/or EP2 and stimulating IL-6 production. These data strongly support the hypothesis that oxLDL-activated DC are the source of high PAFAH levels in atherosclerosis. Platelet activating factor (PAF) is the inflammatory phospholipids for which PAFAH is named. PAF has been shown by other investigators to induce the expression of PAFAH. In our physiologically relevant monocytes, PAF suppresses PAFAH transcription and expression. 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) is a short-chain oxPL that signals through the PAF receptor. Our preliminary data suggest that like PAF, POVPC suppresses PAFAH expression in monocytes. Further investigation into the effects of the short-chain oxPL are warranted. Our data support the hypothesies that oxPL-activated DC are the source of high PAFAH levels in atherosclerosis.

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-04-12T15:30:06Z No. of bitstreams: 1 Juliana Santos Farias.pdf: 1234303 bytes, checksum: 420e49b91acb05fb1346e95075411509 (MD5) / Made available in DSpace on 2017-04-12T15:30:06Z (GMT). No. of bitstreams: 1 Juliana Santos Farias.pdf: 1234303 bytes, checksum: 420e49b91acb05fb1346e95075411509 (MD5) Previous issue date: 2017-03-06 / CAPES, FAPEMA,CNPQ / This paper describes the development of a simple and new sensor electrochemical determination of flutamide in voltamétrica formulations pharmaceutical and artificial urine specimens using a carbon electrode vitreous (ECV) modified with oxidized carbon nanotubes and graphene oxide (NCO-OG), which was named ECV/NCO-OG. Electronic microscopy techniques scanning (SEM) and Raman Spectroscopy were used for the characterization of carbon based materials. The electrochemical response of the analyte front of the ECV/NCO-OG was investigated by cyclic voltammetry techniques (VC) and square wave voltammetry (VOQ). The sensor exhibited a high activity eletrocatalítica for the reduction of flutamide in 0.05 V vs. Ag/AgCl. The parameters experimental influence the response of the electrode was investigated and the optimum conditions were found for the electrode modified with NCO-OG, in Britton-Robinson buffer solution-BR on concentration of 0.1 mol L-1 (pH 5). The proposed sensor presented a wide range of linear response of concentration for the flutamide of 0.1 to 1000 µmol L-1 (or µ g L-1 27.6 to 0.27 g L-1) for n = 15 (R2 = 0.997), limit of detection (LOD), limit of quantification (LOQ), and sensitivity of 0.03 µmol L-1, 0.1 µmol L-1, and 0.30 µmol µA -1 L, respectively. The ECV/NCO-OG was successfully applied to the determination of flutamide in pharmaceutical formulations used in the treatment of prostate cancer and artificial urine samples. The results obtained with the proposed sensor were compared with the method described in the literature and showed a level of 95% confidence, demonstrating that there is no statistical difference between the method of reference and the method proposed. The addition and recovery studies show that the proposed method presents a satisfactory accuracy with average value of 101% recovery ( 1)%. for the fortified samples. / Este trabalho descreve o desenvolvimento de um simples e novo sensor eletroquímico para determinação voltamétrica de flutamida em formulações farmacêuticas e amostras de urina artificial empregando um eletrodo de carbono vítreo (ECV) modificado com nanotubos de carbono oxidado e óxido de grafeno (NCO-OG), o qual foi denominado ECV/NCO-OG. As técnicas microscopia eletrônica de varredura (MEV) e a Espectroscopia Raman foram utilizadas para a caracterização dos materiais à base de carbono. A resposta eletroquímica do analito frente ao ECV/NCO-OG foi investigada através das técnicas de voltametria cíclica (VC) e voltametria de onda quadrada (VOQ). O sensor exibiu uma alta atividade eletrocatalítica para a redução da flutamida em 0,05 V vs Ag/AgCl. Os parâmetros experimentais que influenciam a resposta do eletrodo foram investigados e as condições ótimas foram encontradas para o eletrodo modificado com NCO-OG, em solução tampão Britton-Robinson-BR na concentração de 0,1 mol L-1 (pH 5). O sensor proposto apresentou uma ampla faixa de resposta linear de concentração para a flutamida de 0,1 a 1000 µmol L-1 (ou 27,6 µg L-1 a 0,27 g L-1) para n=15 (R2=0,997), com limite de detecção (LOD), limite de quantificação (LOQ), e sensibilidade de 0,03 µmol L-1, 0,1 µmol L-1, e 0,30 µA µmol-1 L, respectivamente. O ECV/NCO-OG foi aplicado com sucesso para a determinação de flutamida em formulações farmacêuticas utilizadas no tratamento de câncer de próstata e amostras de urina artificial. Os resultados obtidos com o sensor proposto foram comparados com o método descrito na literatura e observou-se um nível de confiança de 95%, demonstrando que não há diferença estatística entre o método de referência e o método proposto. Os estudos de adição e recuperação mostram que o método proposto apresenta uma exatidão satisfatória com valor médio de recuperação de 101% ( 1) %. para as amostras fortificadas.