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No. of bitstreams: 1 correa_vsml_dr_bot.pdf: 3303559 bytes, checksum: 77ee815d6c7fb2eb970233e7f0bf5591 (MD5) Previous issue date: 2020-02-27 O herbicida atrazina (AZ) é um dos mais utilizados, e tem promovido várias alterações sobre os sistemas orgânicos do homem e de outros animais. Esta substância tem sido associada ainda a presença de estresse oxidativo, o qual por vezes é revertido pela associação com antioxidantes, como a vitamina E. Há descrições de várias alterações orgânicas entre elas as respiratórias, e o decréscimo da atividade enzimática da acetilcolinesterase (AChE). No sistema nervoso periférico a AChE é responsável por hidrolisar a acetilcolina (ACh) liberada do terminal nervoso. Na ausência da AChE, o excesso de ACh pode dessensibilizar os receptores de acetilcolina (nAChR) e ao longo de períodos prolongados alterar a organização pós-sináptica diminuindo a força muscular. Assim, este estudo teve por objetivo analisar o efeito protetor da vitamina E sobre a interação neuromuscular e o estresse oxidativo após uso de AZ no músculo diafragma de ratos. Foram utilizados 52 ratos Wistar, machos (CEUA/IBB protocolo 897/2016), adultos. Os animais receberam por 28 dias via gavagem às seguintes substâncias de acordo com os grupos formados: Grupo C: controle (0,3 ml de óleo de milho); Grupo AZ: tratado com atrazina (100 mg/kg); Grupo AZE: atrazina (100 mg/kg) + vitamina E (200 mg/kg); Grupo E: 200 mg/kg vitamina E. Decorrido o período experimental (28 dias) os animais foram anestesiados, eutanasiados e os músculos diafragmas e os nervos frênicos foram dissecados, removidos e processados seguindo os protocolos: a) análise bioquímica da AChE e de marcadores de estresse oxidativo; b) análise morfológica e morfométrica das fibras musculares (HE) e da quantificação da porcentagem de colágeno (Picrossirius Red); c) análise morfológica e morfométrica do nervo frênico; d) análise morfológica e morfométrica das junções neuromusculares (JNMs) através de microscopia de luz e dos nAChR através da microscopia confocal. Os resultados mostraram que a determinação quantitativa da atividade enzimática da AChE foi maior no grupo controle em relação ao grupo AZ. E os menoresvalores foram observados no grupo E. Em relação aos marcadores de estresse oxidativo, o grupo AZ apresentou os maiores valores da catalase, do hidroperóxido de lipídeo, e da Capacidade Antioxidante Hidrofílica; e os menores valores da superóxido dismutase. Diminuição no padrão enzimático dessas enzimas foi observado quando houve associação da AZ com vitamina E. Não houve diferenças entre os grupos em relação à glutationa peroxidase, a morfologia e a morfometria do nervo frênico e na porcentagem de colágeno. Já a área e o diâmetro das fibras musculares foram maiores no grupo E. Mas quando houve associação da vitamina E à AZ, houve diminuição desses parâmetros. Já em relação ao diâmetro das JNMs houve aumento no diâmetro máximo quando a vitamina E foi associada a AZ, embora diferenças morfológicas não tenham sido observadas através da microscopia confocal. A partir desses resultados podemos concluir que a AZ, na dose utilizada, promoveu estresse oxidativo nas fibras musculares do diafragma de ratos. O estresse oxidativo gerado ou mesmo a ação direta da AZ não foi suficiente para promover danos morfológicos sobre a interação neuromuscular estudada (fibras musculares, nervo e junções neuromusculares). Já o estresse oxidativo gerado pela administração subcrônica da AZ foi revertido pelo uso da vitamina E. The herbicide atrazine (AZ) is one of the most used and has promoted several changes on the organic systems of man and other animals. This substance has also been associated with the presence of oxidative stress, which is sometimes reversed by the association with antioxidants, such as vitamin E. There are some descriptions about organic alterations as respiratory and a decrease in the enzymatic activity of acetylcholinesterase (AChE). In the peripheral nervous system, AChE is responsible for hydrolyzing acetylcholine (ACh) released from the nervous terminal. In the absence of AChE, excess ACh can desensitize acetylcholine receptors (nAChR) and, over prolonged periods, alter the postsynaptic organization, decreasing muscle strength. Thus, this study aimed to analyze the protective effect of vitamin E on neuromuscular interaction and oxidative stress after use of AZ in the diaphragm muscle of rats. 52 male Wistar rats (CEUA / IBB protocol 897/2016), adults were used. The animals received for 28 days via gavage the following substances according to the groups formed: Group C: control (0.3 ml of corn oil); AZ group: treated with atrazine (100 mg / kg); AZE Group: atrazine (100 mg / kg) + vitamin E (200 mg / kg); Group E: 200 mg / kg vitamin E. After the experimental period (28 days) the animals were anesthetized, euthanized and the diaphragm muscles and phrenic nerves were dissected, removed and processed following the protocols: a) biochemical analysis of AChE and oxidative stress markers; b) morphological and morphometric analysis of muscle fibers (HE) and quantification of the percentage of collagen (Picrossirius Red); c) morphological and morphometric analysis of the phrenic nerve; d) morphological and morphometric analysis of neuromuscular junctions (NMEs) using light microscopy and nAChR using confocal microscopy. The results showed that the quantitative determination of the enzymatic activity of AChE was greater in the control group compared to the AZ group. There was a significant decrease in group E. Regarding oxidative stress markers, group AZ showed the highest values of catalase, lipid hydroperoxide, and hydrophilic antioxidant capacity; and the lowest values of superoxide dismutase. Decrease in these enzymatic profile was observed after the association between AZ with Vitamin E. There were no differences between groups in relation to glutathione peroxidase, morphology and morphometry of the phrenic nerve and in the percentage of collagen. Muscle fiber area and diameter were greater in group E. But when vitamin E was associated with AZ, these parameters decreased. Regarding the diameter of the NMJs, there was an increase in the maximum diameter when vitamin E was associated with AZ, although morphological differences were not observed through confocal microscopy. From these results we can conclude that AZ, in the dose used, promoted oxidative stress in the muscle fibers of the rat diaphragm. The oxidative stress generated or even the direct action of AZ was not enough to promote morphological damage on the studied neuromuscular interaction (muscle fibers, nerve and neuromuscular junctions). The oxidative stress generated by subchronic AZ administration was reversed by the use of vitamin E.

[eng] Environmental constraints and developmental processes in plants can lead to light energy excess in chloroplasts by lowering the threshold at which light becomes saturating by a lack of electron acceptors in the light-processing structures. Inactivation of photosystems due to high energy quanta is generally known as photoinhibition, a process that can compromise growth and organ development in plants due to an imbalance of the cellular redox state that leads to enhanced oxidative stress. Hence, it is essential to determine environmental factors and stages of organ development that influence the extent of photoinhibition and mechanisms triggered to avoid photoinhibition and cope with photo-oxidative stress, so that plant survival is not put in jeopardy. For this reason, leaves from an ecologically important Mediterranean plant, flowers from a relevant commercial crop and fruits from a highly appreciated agronomic tree, were selected to analyse events leading to photoinhibition and strategies to allow plant acclimation and correct organ development. With this regard, mastic trees were selected to study their sensitivity to cold stress during Mediterranean winters and altitudinal distribution, to determine if antioxidant strategies and leaf phenology influence their ability to survive environmental constraints. On the other hand, lily flowers were selected to study photoinhibitory events taking place during flower opening and how phytohormones could regulate the timing of flower opening by interacting with photo-oxidative stress signals. Besides, sweet cherry fruits were also selected to better understand physiological events related to ripening onset and chloroplast dismantling with the production of antioxidants and hormonal signals involved. Our results show that timing and stage of organ development directly condition the outcomes of photoinhibition with regards of chloroplast status and antioxidants produced, with a general prevailing mechanism where reduced Fv/Fm triggers higher lipid peroxidation and parallel production of phytohormones and antioxidants that deal with increased photo-oxidative stress. In conclusion, photoinhibition does not compromise plant or organ survival, but prompt the activation of signalling networks that promote metabolic changes to fine-tune the timing and severity of this process to allow acclimation and correct organ development.

Objective: The objective of this experiment was to compare conventional antioxidants and plant extracts for oxidative stress control in lambs fed a high-concentrate diet.Methods: Forty-eight male Dorper×Santa Ines lambs with an initial weight of 20±1.49 kg and 60 days of age, were used to evaluate the effects of feeding a combination of Macleaya cordata and Magnolia officinalis plant extracts (0 vs 320 mg/kg dry matter [DM]) in combination with selenium+vitamin E (0 vs 100 IU/kg DM of vitamin E and 0.1 mg/kg DM of selenium) in a completely randomized block design in a 2×2 factorial arrangement. The animals were housed in individual pens and received a high-concentrate diet consisting of 80% whole corn and 20% protein pellet for 60 days. The animals were weighed at the beginning of the experiment and every 14 days for performance monitoring. Three blood samplings were performed during the experimental period for the evaluation of oxidative and protein parameters.Results: The treatments with vitamin E and selenium as additives had a positive influence on final weight, daily weight gain, carcass weight, and selenium content in longissimus muscle (p = 0.01). Plant extracts tended to improve final weight (p = 0.064) and daily weight gain (p = 0.059), showing similar effect as selenium and vitamin E. There was no effect of treatment on blood proteins, indicating that the animals were healthy throughout the experiment.Conclusion: The use of plant extracts had a similar effect as the addition of selenium and vitamin E, with dietary inclusion of additives resulting in better performance of lambs but both supplements did not have strong influence on oxidative stress.

Taurine bulls are highly susceptible to heat stress, leading to increased oxidative stress (OS) and impaired sperm viability. Polyunsaturated fatty acids (PUFAs) supplementation can be an alternative to improve semen quality, which also results in more sperm susceptibility to lipid peroxidation. Moreover, this deleterious effect can be exacerbated in animals affected by heat stress. Vitamin E is a key antioxidant that counteracts lipid peroxidation of sperm membrane caused by OS. Thus, combining PUFAs with vitamin E may improve sperm quality. In this context, this study aimed to evaluate the effect of interaction between PUFAs and vitamin E on sperm quality in Bos taurus bulls under testicular heat stress. Sixteen taurine bulls under testicular heat stress were randomly assigned in four groups: Control, Vitamin E, PUFA, and PUFA + Vitamin E. All groups lasted for 60 days. Samples were cryopreserved/thawed and analyzed for motility variables (CASA), membrane and acrosome integrity, mitochondrial activity, susceptibility to oxidative stress, DNA integrity, and sperm-binding capacity. Results showed that vitamin E had a beneficial effect on some sperm characteristics, whereas PUFA supplementation had an adverse effect when the two treatments were evaluated separately. Finally, the association between PUFAs and vitamin E did not improve sperm quality.

The present study aimed at developing a new vesicular formulation capable of promoting the protective effect of ascorbic acid and tocopherol against intestinal oxidative stress damage, and their efficacy in intestinal wound healing upon oral administration. A pH-dependent copolymer (Eudragit&reg, L100), a water-soluble prebiotic fibre (Nutriose&reg, FM06), a phospholipid mixture (Lipoid S75), and two natural antioxidants (ascorbic acid and tocopherol) were combined to fabricate eudragit-nutriosomes by a simple, solvent-free procedure. The vesicles were spherical and oligolamellar, with some multicompartment structures in Eudragit-nutriosomes, small in size (~100 nm), with highly negative zeta potential. The effect of Eudragit&reg, and Nutriose&reg, on the stability on storage and in simulated gastrointestinal fluids were confirmed by the Turbiscan&reg, technology and in vitro studies, respectively. Eudragit-nutriosomes exhibited a protective effect against H2O2-induced oxidative stress, and a proliferative effect in Caco-2 cells, as they provided the closure of the scratched area after 96 h of incubation.

Dissertação de Mestrado Integrado em Medicina Veterinária A dermatite atópica canina é uma doença que afeta um grande número de animais, sendo que se estima que 10 a 15% da população canina esteja afetada. É uma doença de etiologia multifatorial e de apresentações clínicas diversas, embora haja uma distribuição lesional característica. Recentemente foi demonstrado que o stress oxidativo apresenta um papel importante na dermatite atópica no Homem e também que os níveis serológicos de vitamina E (α-tocoferol), importante antioxidante, encontram-se alterados em cães com a doença. É expectável que cães com a doença menos controlada apresentem um maior stress oxidativo e, assim, níveis serológicos de α-tocoferol inferiores. No presente estudo, foram acompanhados cães com dermatite atópica sob terapêutica com ciclosporina, monitorizados quanto ao estadio clínico através da classificação do prurido, do CADESI-04 e do teor de α-tocoferol em intervalos de 3 semanas. Tanto quando sabemos, este foi o primeiro estudo que avaliou o teor de α-tocoferol ao longo do tempo. Os resultados apresentados revelam que cães saudáveis apresentam um teor de α-tocoferol superior a canídeos com dermatite atópica, o que espelha uma resposta adaptativa que leva à distribuição de α-tocoferol no tecido alvo, reduzindo a sua concentração sérica. Foi possível também sugerir uma associação entre o aumento plasmático de α-tocoferol e a diminuição da classificação do prurido. Este é o sinal clínico da doença que mais afeta a qualidade de vida e contribui indiretamente para o agravamento dos defeitos na barreira cutânea consequentemente facilitando a presença de infeções e o aumento do estado inflamatório, aumentando o stress oxidativo. O controlo do prurido com recurso à ciclosporina resulta então também num maior equilíbrio no consumo de antioxidantes. Não foram encontradas diferenças significativas que permitissem concluir a existência de uma relação entre o teor de α-tocoferol e o CADESI-04. Este estudo permite fundamentar a utilização do α-tocoferol como agente objetivo de monitorização da dermatite atópica canina, o que pode ser particularmente importante se aplicado em estudos de monitorização clínica. Levanta-se ainda a possibilidade lógica do controlo do stress oxidativo, com recurso à suplementação com antioxidantes, como a vitamina E. ABSTRACT - Oxidative stress in canine atopic dermatitis: vitamin E as a biomarker during cyclosporine therapeutics - Canine atopic dermatitis is a disease that affects a large number of animals, as 10 to 15% of the canine population is likely to be affected. It’s a disease with multifactorial aetiology and multiple clinical presentations, although there is a characteristic lesion distribution. It has recently been shown that oxidative stress plays a major role in human atopic dermatitis and the important antioxidant vitamin E (α-tocopherol) plasmatic levels are altered in dogs with the disease. Dogs with less controlled disease are expected to exhibit increased oxidative stress and thus lower α-tocopherol serologic levels. In the present study, dogs with atopic dermatitis were monitored during cyclosporine treatment regarding atopic dermatitis severity using accepted criteria namely: pruritus score and CADESI-04 and also α-tocopherol levels at 3-week intervals. As far as we know, this is the first study to assess α-tocopherol levels over time in canine atopic dermatitis. The results show that healthy dogs have a superior α-tocopherol plasmatic level than dogs with atopic dermatitis, which reflects an adaptive response that leads to α-tocopherol distribution in target tissues, reducing its serological concentration. It was possible to suggest a relation between the increase of α-tocopherol and the reduction of the pruritus score. Pruritus is the hallmark of atopic dermatitis and profoundly affects the life quality and indirectly contributes to skin barrier defects deterioration. This will contribute to yeast and bacteria overgrowth and to increase the inflammatory status, therefore increasing oxidative stress. Controlling pruritus with cyclosporine also results in a better balance regarding antioxidants consumption. No significant differences were found between α-tocopherol levels and CADESI-04 for any time point. This study supports the use of α-tocopherol as an objective mean to monitor canine atopic dermatitis in clinical studies. It’s further suggested that supplementation with antioxidants, such as vitamin E, is relevant for the control of oxidative stress. N/A

Markers of oxidative stress in the hepatopancreas and carotenoid and vitamin E content in the carapace of the invasive crab Percnon gibbesi and the native crab Pachygrapsus marmoratus were compared as indicators of their physiological condition and environmental adaptation. Crabs similar in size were collected from coastal waters of Portals Vells (Mallorca Island, Spain; 39°28’18.79”N, 2°28’19.63”E) at, SI

Background Plasmodium falciparum is sensitive to oxidative stress in vitro and in vivo, and many drugs such as artemisinin, chloroquine and cercosporin interfere in the parasite’s redox system. To minimize the damage caused by reactive radicals, antioxidant enzymes and their substrates found in parasites and in erythrocytes must be functionally active. It was shown that P. falciparum synthesizes vitamin E and that usnic acid acts as an inhibitor of its biosynthesis. Vitamin E is a potent antioxidant that protects polyunsaturated fatty acids from lipid peroxidation, and this activity can be measured by detecting its oxidized product and by evaluating reactive oxygen species (ROS) levels. Results Here, we demonstrated that ROS levels increased in P. falciparum when vitamin E biosynthesis was inhibited by usnic acid treatment and decreased to basal levels if exogenous vitamin E was added. Furthermore, we used metabolic labelling to demonstrate that vitamin E biosynthesized by the parasite acts as an antioxidant since we could detect its radiolabeled oxidized product. The treatment with chloroquine or cercosporin of the parasites increased the ratio between α-tocopherolquinone and α-tocopherol. Conclusions Our findings demonstrate that vitamin E produced endogenously by P. falciparum is active as an antioxidant, probably protecting the parasite from the radicals generated by drugs. Electronic supplementary material The online version of this article (10.1186/s13071-017-2402-3) contains supplementary material, which is available to authorized users.

A dor neuropática (dor devido à lesão no tecido nervoso) é uma condição debilitante, com alta incidência na população mundial. O tratamento dessa condição dolorosa ainda é um grande desafio na clínica devido às ações limitadas dos fármacos atualmente disponíveis e seus consequentes efeitos colaterais. O uso de substâncias com potencial antioxidante no tratamento da dor neuropática vem sendo amplamente discutido devido à participação das espécies reativas de oxigênio e de nitrogênio nessa condição dolorosa. O ácido ascórbico (vitamina C) e o α-tocoferol (vitamina E) representam potentes antioxidantes, os quais são adquiridos por custo relativamente baixo, são bem aceitos pela população, muito utilizados como suplemento alimentar, e parecem possuir algum efeito analgésico, embora esse último efeito tenha ainda muitas questões especulativas e que necessita esclarecimentos. Por estes motivos, o objetivo deste estudo foi avaliar o efeito das vitaminas C e E, administradas isoladas ou juntas, sobre parâmetros nociceptivos, oxidativos e nitrosativos, e proteínas de sinalização intracelular em ratos com constrição no nervo isquiático (CCI, do inglês chronic constriction injury), um modelo de dor neuropática. Após aprovação pelo comitê de ética no uso de animal da UFRGS (#23352), ratos Wistar machos, com idade de 60 dias, foram divididos em 3 grupos experimentais: controle (ratos que não sofreram intervenção cirúrgica), sham (ratos que tiveram o nervo isquiático direito apenas exposto) e CCI (ratos que tiveram o nervo isquiático exposto e esse recebeu 4 amarraduras em seu tronco comum). Cada grupo experimental foi dividido em subgrupos que receberam administração de veículo (salina ou água de beber acrescidas de Tween 80 a 1%), vitamina C (30 mg/kg/dia), vitamina E (15 mg/kg/dia) ou coadministração de vitaminas C+E nas mesmas doses. As administrações foram intraperitoneal ou por via oral, por período de 3 e 10 dias. Os parâmetros nociceptivos utilizados para avaliar sensibilidade mecânica, sensibilidade térmica e recuperação funcional do nervo foram os testes de von Frey eletrônico, teste da placa quente e do índice funcional do isquiático (IFI), respectivamente. Para avaliar o efeito antinociceptivo da administração i.p. dos tratamentos, os parâmetros nociceptivos foram mensurados antes do procedimento cirúrgico, e aos 3, 5, 7 e 10 dias após a lesão nervosa. Ao final dos períodos de 3 e 10 dias, os animais foram mortos por decapitação, e foi coletado plasma, para determinação de indicadores de função hepática e renal (alanina aminotransferase, aspartato aminotransferase, gama GT, bilirrubina e creatinina); fígado, para determinação da morfologia dos hepatócitos e parâmetros oxidativos (hidroperóxidos lipídicos, Glutationa-s-transferase - GST, e capacidade antioxidante total - TAC); nervo isquiático lesionado, para determinação de parâmetros oxidativos (hidroperóxidos lipídicos e TAC); e o segmento lombossacral da medula espinal, para determinação de parâmetros oxidativos (formação de ânion superóxido - SAG, e valores de peróxido de hidrogênio, hidroperóxidos lipídicos, tióis totais, ácido ascórbico e TAC) e nitrosativos (metabólitos do óxido nítrico - NO). O segmento da medula espinal foi usado ainda para determinar a expressão das proteínas de sinalização p38 fosforilada (p-p38), Akt e Akt fosforilada (p-Akt) e do transportador de vitamina C dependente de sódio do tipo 2 (SVCT-2). Foi avaliada ainda, mediante determinação de parâmetros nociceptivos, a duração do efeito antinociceptivo da vitamina C, vitamina E ou vitaminas C+E após o tratamento, o efeito antinociceptivo das vitaminas C+E administradas por via oral, e a coadministração de vitaminas C+E (via oral) concomitante à gabapentina (i.p.), fármaco normalmente utilizado no tratamento de dor neuropática. Os dados de sensibilidade térmica e mecânica foram analisados por ANOVA de medidas repetidas, seguida pelo pós-teste de Tukey. Os demais parâmetros foram avaliados por ANOVA de duas vias (fatores: lesão e tratamento), seguida do pós-teste de Tukey. Os resultados mostraram que vitamina C, vitamina E e vitaminas C+E atenuaram a nocicepção e provocou melhora no IFI tanto aos 3 como aos 10 dias, e que a coadministração das vitaminas induziu efeito antinociceptivo maior do que as mesmas administradas isoladamente em ratos com CCI. O efeito antinociceptivo das vitaminas C+E foi similar, tanto após administração i.p. quanto oral. Também foi observado que o efeito antinociceptivo das vitaminas C, E e C+E durou por várias horas após o término do período de administração de 3 e 10 dias. O uso de vitaminas C+E+gabapentina provocou efeito antinociceptivo maior do que o uso de gabapentina isoladamente. Não foram observadas alterações nos indicadores de função hepática e renal, na morfologia dos hepatócitos e nos parâmetros oxidativos avaliados no tecido hepático. No nervo isquiático lesionado, embora não houve alterações significativas, observou-se acréscimo de 38% na TAC e diminuição de 45% nos hidroperóxidos lipídicos nos animais que receberam vitaminas, comparado aos valores obtidos nos ratos tratados com veículo. Na medula espinal, a administração das vitaminas preveniu a redução nos valores de tióis totais e o aumento na SAG, comparado ao grupo CCI tratado com veículo. Ainda comparado ao grupo veículo, as vitaminas preveniram o aumento nos metabólitos do NO e nos hidroperóxidos lipídicos. A administração de vitaminas C+E também preveniu a redução significativa na expressão do transportador SVCT-2, o aumento nas expressões das proteínas p-p38, p-Akt e Akt, e o aumento no valor do ácido ascórbico, comparado aos ratos CCI que receberam veículo. A administração das vitaminas e a CCI não provocaram alterações significativas na TAC e nos valores de peróxido de hidrogênio na medula espinal. Assim, os resultados mostram que vitamina C, vitamina E e vitaminas C+E, nas doses aqui estudadas, atenuam a dor neuropática e modificam parâmetros oxidativo e nitrosativo, e de sinalização celular, alterados pela CCI. A administração dessas vitaminas não parece provocar toxicidade ao organismo, e poderiam ser uma alternativa como coadjuvante a medicações clássicas usadas no tratamento de condições de dor neuropática. Porém, é necessária a realização de estudos complementares em humanos, dada às diferenças nas respostas à dor em ratos e humanos. Neuropathic pain (pain due to nerve tissue injury) is a debilitating condition, with a high incidence in the world population. The treatment of this painful condition is still a great challenge in the clinic due to the limited actions of the currently available drugs and their consequent side effects. The use of substances with antioxidant potential in the treatment of neuropathic pain has been widely discussed due to the participation of reactive oxygen and nitrogen species in this painful condition. Ascorbic acid (vitamin C) and α-tocopherol (vitamin E) are potent antioxidants, which are obtained by relatively low cost, are well accepted by patients, are widely used as a food supplement, and appear to have some analgesic effect, although this last effect still has many speculative issues and needs clarification. For these reasons, the aim of this study was to evaluate the effect of vitamins C and E, administered alone or together, on nociceptive, oxidative and nitrosative parameters and intracellular signaling proteins in rats with chronic constriction injury (CCI), a model of neuropathic pain. After approval by the ethics committee on animal use of UFRGS (#23352), male Wistar rats, aged 60 days, were divided into 3 groups: control (rats that did not undergo surgery), sham (rats whose right sciatic nerve was only exposed) and CCI (rats whose sciatic nerve was exposed and received 4 ligations in their common trunk). Each experimental group was divided into subgroups that received vehicle injection (saline or drinking water plus Tween 80, 1%), vitamin C (30 mg/kg/day), vitamin E (15 mg/kg/day) or co-administration of vitamins C+E in the same doses. The administrations were by intraperitoneal or oral route, for a period of 3 and 10 days. The nociceptive parameters used to evaluate mechanical sensitivity, thermal sensitivity and nerve functional recovery were the electronic von Frey test, the hot plate test and the sciatic functional index (SFI), respectively. To evaluate the antinociceptive effect of ip administration of vitamin C, vitamin E or vitamins C+E, nociceptive parameters were measured before the surgical procedure and at 3, 5, 7 and 10 days following nerve injury. At the end of the 3 and 10 day periods, the animals were killed by decapitation, and plasma was collected for determination of hepatic and renal function indicators (aspartate aminotransferase, alanine aminotransferase, gamma-GT , bilirubin and creatinine); liver, for determination of hepatocyte morphology and oxidative parameters (lipid hydroperoxides, Glutathione-s-transferase - GST, and total antioxidant capacity - TAC); injured sciatic nerve for determination of oxidative parameters (lipid hydroperoxides and TAC); and the lumbosacral segment of the spinal cord for determination of oxidative (superoxide anion formation - SAG, and values of hydrogen peroxide, lipid hydroperoxides, total thiols, ascorbic acid and TAC) and nitrosative (nitric oxide metabolites - NO) parameters. The spinal cord segment was also used to determine the expression of signaling proteins phosphorylated p38 (p-p38), Akt and phosphorylated Akt (p-Akt), and sodium-dependent vitamin C transporter type 2 (SVCT-2). In addition, it was assessed the duration of the antinociceptive effect of vitamin C, vitamin E or vitamins C+E after end of the treatment, the antinociceptive effect of vitamins C+E by oral route, and the antinociceptive effect of co-administration of vitamins C+E (oral route) concomitant with gabapentin (ip), a drug normally used in the treatment of neuropathic pain. Thermal and mechanical sensitivity data were analyzed by repeated measures ANOVA, followed by Tukey’s post-test. The other parameters were evaluated by two-way ANOVA (factors: injury and treatment), followed by Tukey's post-test. The results showed that vitamin C, vitamin E and C+E vitamins attenuated nociception and improved SFI at both 3 and 10 days, and that a greater antinociceptive effect was induced when vitamins were co-administered than when they were given alone in CCI rats. The antinociceptive effect of vitamins C+E was similar after ip and oral administration. It was also observed that the antinociceptive effect of vitamins C, E and C+E lasted for several hours after the end of the administration period of 3 and 10 days. The use of C+E vitamins+gabapentin caused greater antinociceptive effect than the use of gabapentin alone. . No changes were observed in hepatic and renal function indicators, hepatocyte morphology, and oxidative parameters evaluated in the hepatic tissue. Despite no significant, the injured sciatic nerve showed increase (38%) in TAC and reduction (45%) in lipid hydroperoxides in vitamins-treated CCI rats, compared to rats that received vehicle. In spinal cord, the vitamin administration prevented the reduction in total thiol values and the increase in SAG in CCI animals, compared to vehicle-treated CCI rats. Also compared to vehicletreated CCI rats, the vitamins prevented the increase in NO metabolites and lipid hydroperoxides. The use of vitamins C+E also prevented the significant reduction in SVCT-2 transporter expression, the increase in p-p38, p-Akt, and Akt expressions, and the increase in ascorbic acid levels, compared to CCI rats that received vehicle. Vitamins and CCI did not induce significant changes in TAC and hydrogen peroxide values in the spinal cord. Thus, the results show that vitamins C, E and C+E, in doses used, attenuated neuropathic pain and changed oxidative, nitrosative and cellular signaling parameters modified by CCI. In addition, the use of vitamins does not appear to induce toxicity to the body and could be an alternative as adjuvant to classical medications used in the treatment of neuropathic pain conditions. However, further studies in humans are needed, given the differences in pain responses in rats and humans.

Orientador: Elaine Minatel Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: A distrofia muscular de Duchenne (DMD) é considerada a mais comum e devastadora das distrofias musculares humanas. Inflamação crônica e estresse oxidativo são características marcantes da doença. A Diacereína é uma antraquinona usada no tratamento de osteoartrite, que exibe propriedades anti-inflamatórias e a Vitamina E apresenta um papel importante como potente antioxidante e na preservação da integridade da membrana celular. Com base nas ações desses medicamentos, o objetivo do presente estudo foi avaliar os efeitos da Diacereína e da Vitamina E na mionecrose, no estresse oxidativo e na resposta inflamatória dos músculos diafragma, esternomastóideo e tibial anterior de camundongos mdx. Neste estudo, foram utilizados camundongos das linhagens C57BL/10 e camundongos mdx. Os camundongos mdx foram divididos em 5 grupos: mdx (tratado com solução salina); mdxP (tratado com Prednisona - 5mg/kg; controle positivo); mdxD (tratado com Diacereína ¿ 20mg/kg); mdxVE (tratado com Vitamina E ¿ 40mg/kg) e mdxVED (tratado com Vitamina E e Diacereina). Os camundongos C57BL/10 não receberam nenhum tratamento e foram utilizados como controle. Todos os animais foram submetidos à análise de medida de força. Amostras de sangue foram utilizadas para determinação de creatina quinase (CK) e para a quantificação de IL-1? e IL-6. Os músculos diafragma (DIA), esternomastóideo (STN) e tibial anterior (TA) foram retirados e submetidos à técnicas histológicas (HE; IgG; F4/80; DHE e lipofuscina), Western blotting (TNF-?, NF-?B, 4-HNE, SOD2, Catalase, GR) e para determinação da atividade da GSH. Os resultados demonstraram que os camundongos mdx tratados com Diacereína, Vitamina E e/ou com associação desses dois medicamentos apresentaram redução da perda da força, do dano muscular, da resposta inflamatória exacerbada e dos danos oxidativos. Em comparação com o tratamento com Prednisona, os resultados demonstraram que o tratamento com Diacereína e Vitamina E melhoraram o fenótipo distrófico dos músculos analisados, semelhante ao observado no tratamento com o glicocorticoide. Em conjunto, os resultados demonstraram os efeitos benéficos do tratamento com Diacereína e Vitamina E, administrados isoladamente ou em associação, sobre o processo de regeneração muscular, resposta inflamatória e estresse oxidativo nos músculos DIA, STN e TA de camundongos mdx Abstract: Duchenne muscular dystrophy (DMD) is considered the most common and devastating of human muscular dystrophies. Chronic inflammation and oxidative stress are striking features of disease. Diacerein is an anthraquinone used in the osteoarthritis treatment, which exhibits anti-inflammatory and antioxidant properties and the Vitamin E presents an important role as a potent antioxidant and in preserving the integrity of the cell membrane. The aim of the present study was evaluated the effects of Diacerein and Vitamin E against myonecrosis, oxidative stress and inflammatory response in the diaphragm, sternomastoid and tibialis anterior muscles of mdx mice. In this study, C57BL/10 and mdx mice were used. The mdx mice were randomly divided into 5 groups: mdx (treated with saline); mdxP (treated with Prednisone ¿ 5mg/kg; positive control); mdxD (treated with Diacerein ¿ 20mg/kg); mdxVE (treated with Vitamin E ¿ 40mg/kg) and mdxVED (treated with Vitamin E and Diacerein). The C57BL/10 mice received no treatment and were used as a control group. All animals were submitted to force measurement analysis. Blood samples were used for the determination of creatine kinase (CK) and for the quantification of IL-1? and IL-6 levels. The diaphragm (DIA), sternomastoid (STN) and tibialis anterior (TA) muscles were removed and submitted to histological techniques (HE, IgG, F4/80, DHE and lipofuscin), Western blotting (TNF-?, NF-?B, 4-HNE, SOD2, Catalase, GR) and for the determination of GSH activity. The results showed that mdx mice treated with Diacerein, Vitamin E and/or association of these two drugs presented a reduction in strength loss, muscle damage, exacerbated inflammatory response and oxidative damage. Compared with Prednisone treatment, the results demonstrated that treatment with Diacerein and Vitamin E improved the dystrophic phenotype of the muscles analyzed, similar to that observed with glucocorticoid treatment. Taken together, the results demonstrate the beneficial effects of treatment with Diacerein and Vitamin E, administered alone or in combination, in the process of muscle regeneration, inflammatory response and oxidative stress in the DIA, STN and TA muscles of mdx mice Doutorado Anatomia Doutor em Biologia Celular e Estrutural FAPESP 2014/01970-6 CNPQ 147862/2014-0 CAPES

Objectives The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity. Methods C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group) or without (O group) vitamin E supplementation. Results O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT) and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01). ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance. Conclusions This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.

FUNDAMENTO: A doença de Chagas continua a ser uma importante doença endêmica no país, sendo o acometimento cardíaco a sua manifestação mais grave. OBJETIVO: Verificar se o uso concomitante de carvedilol potencializará o efeito antioxidante das vitaminas E e C na atenuação do estresse oxidativo sistêmico na cardiopatia chagásica crônica. MÉTODOS: Foram estudados 42 pacientes com cardiopatia chagásica, agrupados de acordo com a classificação modificada de Los Andes, em quatro grupos: 10 pacientes no grupo IA (eletrocardiograma e ecocardiograma normais: sem envolvimento do coração), 20 pacientes do grupo IB (eletrocardiograma normal e ecocardiograma anormal: ligeiro envolvimento cardíaco), oito pacientes no grupo II (eletrocardiograma e ecocardiograma anormais, sem insuficiência cardíaca: moderado envolvimento cardíaco) e quatro pacientes no grupo III (eletrocardiograma e ecocardiograma anormais com insuficiência cardíaca: grave envolvimento cardíaco). Os marcadores de estresse oxidativo foram medidos no sangue, antes e após um período de seis meses de tratamento com carvedilol e após seis meses de terapia combinada com vitaminas E e C. Os marcadores foram: atividades da superóxido dismutase, catalase, glutationa peroxidase, glutationa S-transferase e redutase, mieloperoxidase e adenosina deaminase, e os níveis de glutationa reduzida, de espécies reativas do ácido tiobarbitúrico, proteína carbonilada, vitamina E e óxido nítrico. RESULTADOS: Após o tratamento com carvedilol, todos os grupos apresentaram diminuições significativas dos níveis de proteína carbonilada e glutationa reduzida, enquanto os níveis de óxido nítrico e atividade da adenosina aumentaram significativamente apenas no grupo menos acometido (IA). Além disso, a maioria das enzimas antioxidantes mostrou atividades diminuídas nos grupos menos acometidos (IA e IB). Com a adição das vitaminas ao carvedilol houve diminuição dos danos em proteínas, nos níveis de glutationa e na maior parte da atividade das enzimas antioxidantes. CONCLUSÕES: A queda dos níveis de estresse oxidativo, verificada pelos marcadores testados, foi mais acentuada quando da associação do fármaco carvedilol com as vitaminas antioxidantes. Os dados sugerem que tanto o carvedilol isoladamente como sua associação com as vitaminas foram eficazes em atenuar o dano oxidativo sistêmico em pacientes com CC, especialmente aqueles menos acometidos, sugerindo a possibilidade de sinergismo entre esses compostos. BACKGROUND: Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. OBJECTIVE: To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. METHODS: A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. RESULTS: After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. CONCLUSIONS: The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.

CONTEXT: Diabetes mellitus is a disease characterized by hyperglycemia that, when allowed to progress long-term untreated, develops vascular and neurological complications, which are responsible for the development of alterations in the enteric nervous system in diabetic patients. In the gastrointestinal tract, diabetes mellitus promotes motor and sensory changes, and in the reflex function of this system, causing gastroparesis, diarrhea, constipation, megacolon, slow gastrointestinal transit, gastric stasis and dilation with decreased or increased peristaltic contractions. Several studies have shown that oxidative stress is the main responsible for the vascular and neurological complications affecting the enteric nervous system of diabetics. OBJECTIVE: The effects of 0.1% and 2% vitamin E on myosin-V- and nNOS-immunoreactive neurons in the jejunum of diabetic rats were investigated. METHODS: Thirty rats were divided into the groups: normoglycemic, normoglycemic treated with 0.1% vitamin E, normoglycemic treated with 2% vitamin E, diabetic, diabetic treated with 0.1% vitamin E, and diabetic treated with 2% vitamin E. The neuronal density and areas of neuron cell bodies were determined. RESULTS: Diabetes (diabetic group) significantly reduced the number of myosin-V-immunoreactive neurons compared with the normoglycemic group. The diabetic treated with 0.1% vitamin E and diabetic treated with 2% vitamin E groups did not exhibit a greater density than the D group (P>0.05). Nitrergic density did not change with diabetes (P>0.05). The areas of myosin-V- and nNOS-immunoreactive neurons significantly increased in the normoglycemic treated with 2% vitamin E and diabetic groups compared with the normoglycemic group. CONCLUSION: Supplementation with 2% vitamin E had a neurotrophic effect only in the area of myosin-V-immunoreactive neurons compared with the diabetic group.

Background There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. Objectives To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. Search methods We searched the Cochrane Schizophrenia Group’s Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. Data collection and analysis We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. Main results The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. Authors' conclusions Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.

Evidence of oxidative stress in horses has been described in reports dealing with intense and endurance exercise. Oxidative stress occurs when antioxidant systems are insufficient causing oxidation to potentially damage DNA, proteins, and lipids, and contribute to degenerative changes. Vitamin E is the most commonly supplemented antioxidant in horses and has been shown that horses in exercise conditioning may require higher intakes of vitamin E than recommended. Also in various species vitamin C potentiates the effects of vitamin E; however, under maintenance conditions horses have the ability to synthesize sufficient ascorbate, the demand increases as stress on the body is increased. Competitive endurance horses were estimated to consume 1.2 to 5-times higher levels of vitamin E than recommended intakes. In these horses a negative correlation was found between the vitamin E intake and creatine kinase, and aspartate aminotransferase. Similarly, three-day event horses have vitamin E average intakes about 50% over recommended levels, and it was also found that intake of vitamin E negatively correlated with inflammatory markers. However, large doses of vitamin E at about 10-times the recommended levels could potentially interfere with beta-carotene absorption. While some studies have shown benefits of lipoic acid supplementation in endurance trained horses similar to that of vitamin E, other studies failed to show any benefit of supplemental superoxide dismutase in intensely exercising horses. The implications from this broad scope of work show potential benefits for supplementing various antioxidants however, before assuming efficacy from other species horse specific studies should be performed. Evidência de estresse oxidativo em eqüinos tem sido descrita em artigos que lidam com exercícios intensos e de resistência. O estresse oxidativo ocorre quando sistemas antioxidantes são insuficientes, causando oxidação com potencial de danificar DNA, proteínas e lipídios, e contribui para mudanças degenerativas. A vitamina E é o antioxidante mais comumente suplementado em cavalos e tem sido demonstrado que cavalos em exercício condicionado podem exigir maior consumo dessa vitamina que o recomendado. A vitamina C também potencializa o efeito da vitamina E em várias espécies. No entanto, sob condições de mantença, os cavalos têm capacidade de sintetizar ácido ascórbico suficiente, a demanda aumenta enquanto o estresse sobre o corpo aumenta. Foi estimado para cavalos de competição (corrida) um consumo de 1,2 até 5 vezes os níveis de vitamina E recomendados para ingestão. Há correlação negativa entre a ingestão de vitamina E, creatinina quinase e aspartato aminotransferase nesses cavalos. Do mesmo modo, cavalos participantes de competições de três dias ingerem em média 50% a mais dos níveis recomendados de vitamina E. Apurou-se, também, que a ingestão de vitamina E é negativamente correlacionada com marcadores inflamatórios. No entanto, grandes doses de vitamina E, cerca de 10 vezes o recomendado, poderiam interferir na absorção de beta-caroteno. Embora alguns estudos têm mostrado que os benefícios da suplementação de ácido lipóico na resistência de cavalos treinados são semelhantes aos da vitamina E, outros estudos não mostraram nenhum benefício da suplementação com superóxido desmutase, em exercícios intensos de cavalos. As implicações deste vasto campo de trabalho mostram os benéficos potenciais para suplementação de vários antioxidantes, no entanto, antes de se comprovar a eficácia, devem ser realizados estudos específicos em outras espécies de cavalos.

OBJETIVO: comparar marcadores séricos de estresse oxidativo entre pacientes inférteis com e sem endometriose e avaliar a associação destes marcadores com o estadiamento da doença. MÉTODOS: estudo prospectivo envolvendo a inclusão consecutiva de 112 pacientes inférteis, não-obesas, com idade inferior a 39 anos, divididas em dois grupos: Endometriose (n=48, sendo 26 com endometriose mínima e leve - Estádio I/II e 22 com endometriose moderada e grave - Estádio III/IV) e Controle (n=64, com fator tubário e/ou masculino de infertilidade). Durante a fase folicular precoce do ciclo menstrual, foram coletadas amostras sanguíneas para análise dos níveis séricos de malondialdeído, glutationa e níveis totais de hidroperóxidos, por espectrofotometria e vitamina E, por cromatografia líquida de alto desempenho. Os resultados obtidos foram comparados da seguinte forma: os grupos endometriose versus controle; endometriose estádio I/II e controle, endometriose estádio III/IV e controle e entre os dois subgrupos de endometriose. Em todas as análises, foi considerado o nível de significância de 5% (p

The aims of this study were to determine the effects of acetylsalicylic acid (ASA) on inflammation and oxidative stress markers in hemodialysis (HD) patients and to examine the associations between these markers and the sociodemographic and clinical characteristics of participants. The study included 36 subjects who used 300 mg of ASA for 60 days. Inflammation and oxidative stress were assessed based on levels of biochemical markers. ASA usage promoted a decrease in high-sensitivity C-reactive protein (p = 0.01). The level of hydrogen peroxide increased after 30 days of use of ASA and subsequently decreased (p = 0.01). Reduced glutathione reduced at the end of the study (p 0.01); the malondialdehyde level did not change and the levels of vitamins A and E were inverse to drug use (p = 0.01). ASA usage promoted reduced levels of inflammation, increased production of markers of oxidative stress, and reduced antioxidant defense.

Background Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population. Methods A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays. Results The AO group had higher 8-Oxo-2′-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression. Conclusions WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0652-4) contains supplementary material, which is available to authorized users.

Una de les teories sobre l'envelliment més acceptades en animals i humans és la teoria dels radicals lliures que descriu l'augment d'estrès oxidatiu a mesura que augmenta l'edat de l'organisme. Desafortunadament, hi ha pocs estudis que demostrin aquesta teoria en les plantes, i cap d'ells en plantes de gran longevitat. En aquesta tesi vam escollir dos models de plantes perennes de gran longevitat per tal d'investigar la importància de l'estrès oxidatiu, juntament amb els mecanismes de protecció com la vitamina E, en els processos d'envelliment de les plantes sota les condicions climàtiques naturals dels hàbitats on creixen. Per tal de dur a terme aquest objectiu es va analitzar l'efecte de l'edat (en un rang d'edats d'l a 280 anys) sobre el grau de peroxidació lipídica, els mecanismes de fotoprotecció i altres marcadors d'estrès oxidatiu en fulles i tubercles (l'òrgan perenne) utilitzant com a model l'herbàcia perenne no clonal més longeva registrada fins a l'actualitat, Borderea pyrenaica, en la que també es va investigar el possible efecte del sexe en els processos d'envelliment. L'altre espècie, Vellozia gigantea, es tracta d'una planta endèmica del Brasil que tot i no poder ésser datada, es considera que pot arribar a tenir més de 500 anys. En aquest cas es va avaluar l'efecte del tamany, intrínsec a l'edat, en els marcadors d'estrès oxidatiu i també es va estudiar la resposta ecofisiològica a les variacions estacionals (estació seca i plujosa). Els resultats dels diferents treballs realitzats mostren que l'edat o el tamany de la planta no té un efecte negatiu en els processos fisiològics mesurats en termes d'estrès oxidatiu, mostrant doncs que la teoria dels radicals lliures no és universal en plantes perennes. B. pyrenaica no presenta signes de deteriorament fisiològic amb l'edat, almenys fins a l'edat estudiada (280 anys). A més, les femelles centenàries de B. pyrenaica presenten una major capacitat de fotoprotecció que els mascles de la mateixa edat i les plantes juvenils, per això es proposa que aquesta espècie presenta senescència negativa. L'òrgan perenne subterrani de B. pyrenaica (els tubercles) sembla ser el secret de la seva extraordinària longevitat, considerant la seva peculiar estratègia de creixement juntament amb el seu eficient mecanisme de protecció antioxidant en vitamina E que augmenta amb l'edat (senescència negativa). En la planta arborescent V. gigantea no només les plantes de major tamany van mostrar una eficient homeòstasi hídrica i nutricional, almenys igual d'eficient que les de menor tamany; sinó que els nivells de vitamina E, important mecanisme de protecció contra l'estrès oxidatiu, van ser significativament més alts en les plantes de major tamany. L'absència de deteriorament fisiològic amb l'augment del tamany i, així doncs de l'edat, revela senescència negligible en V. gigantea. A més s’observa que tant els tocotrienols (per primera vegada detectats en fulles en plantes superiors) com els tocoferols (vitamina E) tenen un paper important de protecció contra l’estrès foto-oxidatiu. Durant les condicions de dèficit hídric de l’estació seca, V. gigantea desenvolupa un eficient mecanisme de protecció, basat en el tancament estomàtic per conservar l’aigua en la planta induït per l’àcid abscísic, que a més, indueix presumiblement la síntesi de vitamina E per protegir de l’estrès oxidatiu. En aquests estudis es conclou que les plantes perennes són organismes altament resistents a l’estrès i l’envelliment, tal com es mostra en els mecanismes de protecció que desenvolupen per a mantenir les seves funcions fisiològiques fins edats molt avançades, observant que ni l’edat ni el tamany de la planta és la causa principal del declivi funcional de l’organisme., One of the most accepted theories of ageing in animals and humans is the free radical theory of ageing, which describes that oxidative stress increases with age. Unfortunately, there are very few studies that test this theory in plants, and none in long-lived perennial plants. In this thesis, we choose two models of long-lived perennial plants to investigate the processes of ageing and the importance of oxidative stress, along with the role of protection mechanisms such as vitamin E, in the ageing process in plants under natural climatic conditions. With this aim, we explored the effects of age (ranging from 1 to 280 years) in the extent of lipid peroxidation, photoprotection mechanisms and other oxidative stress markers in leaves and tubers (perennial organ) in the longest-lived perennial — not clonal — herb registered to date, Borderea pyrenaica. The other species used in the study, Vellozia gigantea, is an endemic plant of Brazil in which it is not possible estimate its age, but it is considered to live more than 500 years. In this species, we evaluated the effect of size on various oxidative stress markers and evaluated the ecophysiological response to seasonal variations in water availability (rainy and dry season) in plants grown in their natural habitat. Results show that neither age nor size have a negative effect on plant physiological processes related to oxidative stress, thus suggesting that the free radical theory of ageing is not universal in perennials plants. B. pyrenaica showed absence of physiological deterioration with aging as indicated by oxidative stress markers, at least until the studied age (280 years), showing that the oldest females display a greater photoprotection than males of the same age and juveniles (negative senescence). The perennial organ that grows underground in B. pyrenaica (tubers) seems to be the secret of its long life, considering its unique growth strategy together with its efficient antioxidant protection mechanism (vitamin E), whose levels increased with age. V. gigantea also shows absence of physiological deterioration with ageing (mature individuals of various sizes were examined), which was also associated with increasing vitamin E levels in the oldest individuals, suggesting therefore a case of negligible senescence. In this plant species, tocotrienols were found in leaves (this is the first documented study showing tocotrienols in leaves of higher plants), which might have an important role to protect against photo-oxidative stress, along with tocopherols. Water deficit conditions during the dry season led V. gigantea to activate an efficient protection mechanism based on abscisic acid-induced stomatal closure to prevent water loss and presumably increase vitamin E biosynthesis. In this thesis, it is concluded that perennials plants are highly resistant organisms to stress and ageing, as shown by their protective mechanisms to maintain adequate physiological functions until very advanced ages, so that neither age nor size cause any functional decline in the organism.

La esteatohepatitis no alcohólica se caracteriza histológicamente por el balonamiento de los hepatocitos, la inflamación lobulillar y la esteatosis. Al sospechar este diagnóstico es importante la exclusión de otras causas de lesión hepática principalmente el consumo excesivo de alcohol; sin embargo, la biopsia es el único método disponible hasta el momento para confirmar el diagnóstico. Para el tratamiento de esta enfermedad, la vitamina E debe ser considerada una terapia de primera línea debido a que en diversos ensayos clínicos se ha observado que aunque sin un impacto significativo en la fibrosis, a dosis de 800 UI día mejora la histología en adultos no diabéticos con NASH confirmado por biopsia. A pesar de los beneficios demostrados con el uso de este medicamento se debe tener en cuenta que no reemplaza los cambios en la dieta y el ejercicio, y que por el contrario, representa un complemento a estas medidas Nonalcoholic Steatohepatitis (NASH) is characterized histologically by the ballooning of hepatocytes, lobular inflammation and steatosis. If this diagnosis is suspected, it is important to exclude other causes of liver damage, especially excessive consumption of alcohol. Nevertheless, to date, a biopsy is the only method available to confirm the diagnosis. Vitamin E should be considered a first-line therapy for treatment of this disease because several clinical studies have shown that a dose of 800 UI/day improves the histology of non-diabetic adults suffering from NASH even when there is no significant impact on fibrosis. These results were confirmed by biopsies. Despite the proven benefits of the use of this drug, it is important to be aware that its use cannot replace changes in diet and exercise but rather should be seen as a complement to these measures

O capim Brachiaria sp. trazido para o Brasil na revolução verde, veio com o objetivo de aumentar a produção pecuária brasileira. Juntamete com o capim, começararam a surgir problemas, como a cigarrinha das pastagens e a fotossenssibilização hepatógena. A etiologia da fotossenssibilização causada pelo capim Brachiaria sp. ainda é controversa. Mas mesmo não sabendo ao certo se o causador é as saponinas esteroidais ou o fungo Phytomices chartarium, sabese que elas ocorrem, e causam prejuízos à pecuária. As alterações laboratoriais descritas são o aumento de atividade das enzimas aspartato aminotransferase (AST) e gama glutamiltransferase (GGT), bilerrubinemia e icterícia, além de indícios de insuficiência da função hepática. Os exames histopatológicos podem demonstrar uma colangiohepatite e presença de macrófagos espumosos. A presença destas células é importante, pois a sua quantificação foi correlacionada negativamente com o ganho em peso de bovinos. Desta forma, o objetivo deste estudo foi avaliar 40 tourinhos nelore, com o consumo de feno de Brachiaria sp. ajustado para a maior quantidade possível de volumoso (84%), no intuto de reproduzir as alterações hepáticas descritas em casos de fotossensibilização hepatógena, que foram monitoradas por meio de testes como o perfil metabólico e histológico do fígado e linfonodos, e ainda verificar se os antioxidantes ofertados seriam capazes de minimizar estas alterações, promovendo maior desenvolvimento ponderal e melhorando as características da carcaça de bovinos confinados. Como resultados, o feno de braquiaria com baixas quantidades de saponina e de esporos do fungo, não induziram sinais clínicos de lesão hepática nos tourinhos. Porém as avaliações laboratoriais indicam evidencias de alteração hepática inflamatória crônica com presença de macrófagos espumosos. A suplementação com antioxidantes não alterou o perfil metabólico dos animais, mas reduziu a quantidade dos macrófagos espumosos no fígado. Essa diminuição não melhorou o desenvolvimento ponderal dos bovinos, as características de carcaça e a qualidade final da carne. The grass Brachiaria sp. brought to Brazil in the green revolution, came with the goal of increasing the Brazilian livestock production. The introducing of the grass, starts emerging problems such as leaf hopper pastures and hepatogenous photosensitization. The etiology of photosensitization caused by Brachiaria sp. is still controversial. But not even knowing for sure rightly if the cause is the steroidal saponins or the fungus Phytomices chartarium, it is known that they occur and cause damage to livestock. The described laboratory abnormalities are increased activity of enzymes aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT), bilerrubinemia and jaundice, and evidence of insufficient functionof.liver. Histopathological examination can demonstrate a cholangiohepatitis and presence of foamy macrophages. The presence of these cells is important because its quantification was negatively correlated with the gain in cattle weight. Thus this study evaluated 40 Nelore young bulls, with the Brachiaria sp hay consumption adjusted to the maximum amount of forage (84%), with the goal of reproducing the hepatic abnormalities described in cases of photosensitization. Therefore, the aim of this study was to evaluate the possible liver changes, by the metabolic and histological profile of the liver and lymph nodes, and also check if the offered antioxidants would be able to minimize these changes, promoting greater weight gain and improving carcass characteristics of feedlot cattle. As a result, the braquiaria hay with low amounts of saponin and fungal spores did not induce clinical signs of liver damage in young bulls, but laboratory assessments indicate evidence of chronic inflammatory liver change with the presence of foamy macrophages. The antioxidant supplementation did not alter the metabolic profile of the animals, but reduced the amount of foamy macrophages in the liver. However this decrease did not improve weight gain of cattle, carcass characteristics and the final quality of the meat. Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq

Os antioxidantes apresentam efeito benéfico sobre a função endotelial e neuroprotetora em humanos e animais, participando na prevenção e tratamento de doenças isquêmicas cerebrais. A utilização da vitamina E e de fenóis da casca do pequi (Caryocar brasiliense) são promissores na ação antioxidante nestas doenças. Dessa forma, este trabalho teve o objetivo de verificar o efeito da suplementação com extrato etanólico da casca de pequi (C. brasiliense) na disfunção cerebral em ratos após indução de isquemia global transitória e reperfusão. Para tal, foram utilizados 100 ratos distribuídos aleatoriamente em cinco grupos de 20 indivíduos, que receberam veículo oleoso (grupo controle), extrato etanólico da casca de pequi nas doses 100, 300 e 600 mg/kg de peso (grupos 2, 3 e 4) e 300mg/kg de vitamina E (grupo 5). Os ratos foram suplementados por 30 dias anteriores ao procedimento cirúrgico. Os 20 animais de cada grupo foram subdivididos em momentos (subgrupos) de isquemia de 5, 20 e 45 minutos por oclusão bilateral das artérias carótidas comuns e subgrupo sem isquemia, todos com reperfusão de duas horas. Foram colhidas amostras de cérebro para as análises histológica e imunoistoquímica, sendo utilizados os anticorpos anti-caspase-3 clivada, anti-fosfo-ERK1/2 e anti-fosfo-JNK. No grupo controle, as lesões histológicas, a expressão de caspase-3 clivada, de fosfo- ERK1/2 e de fosfo-JNK progrediram de acordo com o aumento do tempo isquemia. O extrato etanólico da casca de pequi, principalmente nas doses de 300 e 600mg/kg, reduziu o número de neurônios isquêmicos em cérebros de ratos submetidos à isquemia transitória global e reperfusão. Apesar de não haver diferença significativa entre os grupos, o extrato etanólico da casca de pequi reduziu a expressão de caspase-3 clivada e de fosfo-ERK1/2 em relação ao grupo controle e apresentou indícios de aumentar a expressão de fosfo-JNK entre os grupos. Os suplementos utilizados mostraram-se promissores para reduzir as lesões precoces de isquemia e reperfusão cerebral. Dessa forma, conclui-se que o extrato etanólico da casca de pequi possui ação neuroprotetora após lesão de isquemia global transitória e reperfusão em ratos.

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2020-07-23T21:35:42Z No. of bitstreams: 1 2011 - Waldsylvio da Silva Vieira.pdf: 643809 bytes, checksum: dc29fef3828fdeb78cac3da2540b5bad (MD5) Made available in DSpace on 2020-07-23T21:35:42Z (GMT). No. of bitstreams: 1 2011 - Waldsylvio da Silva Vieira.pdf: 643809 bytes, checksum: dc29fef3828fdeb78cac3da2540b5bad (MD5) Previous issue date: 2011-01-26 Horses have great ability to transport oxygen, however, situations of excessive physical effort in sports activities, leading to conditions of oxidative stress with potential for developing injuries that affect primarily the muscles of these animals. With the aim of evaluating biochemical and oxidatives changes and exercise-induced in plasma of horses and the effect of supplementation of selenium (Se) and vitamin E on these parameters, 16 horses were divided into two groups, one being supplemented by 20 days and vitamin E and the second control group. They attended a polo game so to reproduce the conditions of competition. Have not been highlighted significant differences between groups, but the treated group showed less variation in serum creatinine levels after the game, the enzyme activity of serum AST presented significant variation in animals and control group remained stable for the treated group, the enzyme CK amounted in both groups, but remained high within 72 h in the tracking group. The largest plasma lactate variation was observed in the tracking group differing basal value already after the first game time. The total antioxidant capacity fell shortly after the first game time, returning to basal value after 24 hours. Not observed difference between groups. We conclude that supplementation with selenium and vitamin E promoted a increased resistance to muscular injury in the treated animals, but did not affect the total antioxidant capacity in the treated group compared with the control group. Os cavalos apresentam grande capacidade de transporte de oxig?nio, no entanto, situa??es de esfor?o f?sico excessivo em atividades esportivas, levam a condi??es de estresse oxidativo com potencial para o desenvolvimento de les?es, que afetar?o principalmente os m?sculos destes animais. Com o intuito de avaliar as altera??es bioqu?micas e oxidativas induzidas pelo exerc?cio no plasma de cavalos atletas e o efeito da suplementa??o de sel?nio (Se) e vitamina E sobre estes par?metros, 16 equinos foram divididos em dois grupos, sendo um suplementado por 20 dias com Se e vitamina E e o segundo grupo testemunha. Estes animais participaram de um jogo de polo de modo a reproduzir as condi??es de competi??o. N?o foram evidenciadas diferen?as significativas entre os grupos, por?m o grupo tratado apresentou menor varia??o nos n?veis s?ricos de creatinina ap?s o jogo, a atividade s?rica da enzima AST apresentou varia??o significativa nos animais do grupo controle e permaneceu est?vel para o grupo tratado, a enzima CK elevou-se em ambos os grupos, mas permaneceu elevada at? 72 h no grupo controle. A maior varia??o de lactato plasm?tico foi observada no grupo controle diferindo do valor basal j? ap?s o primeiro tempo de jogo. A capacidade antioxidante total reduziu-se logo ap?s o primeiro tempo de jogo, retornando aos valores basais ap?s 24 horas. N?o se observou diferen?a entre os grupos. Conclu?mos que a suplementa??o com Se e Vitamina E promoveu maior resist?ncia ao dano muscular nos animais tratados, por?m n?o alterou a capacidade antioxidante total do grupo tratado comparado ao grupo controle.

The effects of vitamins C and/or E associated to amonium tetrathiomolybdate (TTM) in the treatment of cumulative copper intoxication (ICC) in sheep were analyzed throughout oxidative metabolism. Reduced glutathione (GSH), malondialdehyde (MDA), uric acid and the ferric reducing ability of plasma (FRAP) concentrations were evaluated. Twenty four male sheep, Santa Ines breed, with 25 kg BW was distributed in four treatments: TTM, TTM and vitamin C (TTM+VC), TTM with vitamin E (TTM+VE) and TTM with vitamins C and E (TTM+VCE). The intoxication status caused an intensive formation of free radicals with reduction of the GSH concentration and increase of MDA. Despite the increase in the capacity of plasmatic antioxidant observed with the increase of uric acid and FRAP concentrations, it was not observed any benefit with treatments using oxidant vitamins, isolatedly or together with classic treatment only with TTM. Para avaliar o efeito da utilização parenteral das vitaminas C e/ou E associadas ao quelante de cobre, tetratiomolibdato de amônio (TTM), no tratamento de ovinos com intoxicação cumulativa por cobre (ICC), foram analisados o metabolismo oxidativo, através das concentrações sanguíneas de glutationa reduzida (GSH), séricas de malondialdeído (MDA) e ácido úrico, e a habilidade de redução férrica plasmática (HRFP) desses animais. Foram utilizados 24 ovinos machos, da raça Santa Inês, com peso médio de 25 kg e distribuídos em quatro tratamentos: TTM, TTM e vitamina C (TTM+VC), TTM e vitamina E (TTM+VE) e TTM e vitaminas C e E (TTM+VCE). O quadro de intoxicação cúprica provocou intensa formação de radicais livres, com redução da concentração de GSH e aumento do MDA, apesar do aumento na capacidade antioxidante plasmática, decorrente do aumento da concentração de ácido úrico e da HRFP. Não foi observado benefício algum da utilização das vitaminas antioxidantes, isoladamente ou associadas, com o tratamento clássico baseado na administração de TTM, na redução do estresse oxidativo.

Chronic chagasic cardiac patients are exposed to oxidative stress that apparently contributes to disease progression. Benznidazole (BZN) is the main drug used for the treatment of chagasic patients and its action involves the generation of reactive species. 41 patients with Chagas' heart disease were selected and biomarkers of oxidative stress were measured before and after 2 months of BZN treatment (5 mg/kg/day) and the subsequent antioxidant supplementation with vitamin E (800 UI/day) and C (500 mg/day) during 6 months. Patients were classified according to the modified Los Andes clinical hemodynamic classification in groups IA, IB, II and III, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the contents of reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), protein carbonyl (PC), vitamin E and C and nitric oxide (NO), myeloperoxidase (MPO) and adenosine deaminase (ADA) activities were measured in their blood. Excepting in group III, after BZN treatment SOD, CAT, GPx and GST activities as well as PC levels were enhanced while vitamin E levels were decreased in these groups. After antioxidant supplementation the activities of SOD, GPx and GR were decreased whereas PC, TBARS, NO, and GSH levels were decreased. In conclusion, BZN treatment promoted an oxidative insult in such patients while the antioxidant supplementation was able to attenuate this effect by increasing vitamin E levels, decreasing PC and TBARS levels, inhibiting SOD, GPx and GR activities as well as inflammatory markers, mainly in stages with less cardiac involvement.

Exposure to arsenic occurs mainly via drinking water and, in some situations, via polluted foods, inhalation, and cutaneous absorption. Natural, industrial, and antrophical processes have been contributing to increased levels of arsenic in the environment. Arsenic affects male reproductive functions, affecting the spermatogenic process, and there is a lot of evidence that indicates its poisonous action is related to increased production of reactive species of oxygen. These harmful effects can be minimized by the administration of several substances, including amino acids, vitamins and quelants compounds. Guaraná, a plant typical of the Amazonian area, is rich in caffeine, flavonoyds and tannins with antioxidant properties, used in Phitoterapy for the prevention and the treatment of diseases associated with the unbalance of the cell's oxidant activity. Vitamin E suppresses lipidic peroxidation in the testes and mithocondria and is capable of reverting current harmful effects of the testicular exposure to several factors such as ozone, ciclofosfamide, toxins and policlorate bifenilics pollutants. The present work evaluated the capacity of the testes and other tecidual structures to accumulate arsenic and the current poisonous effects of that accumulation, as well as the antioxidant potential of guarana and vitamin E. 35 seventy- day-old Swiss mice were used. They were divided in five groups containing seven animals each: CTR - (negative control) in which the animals just received distilled water and 0,5 mL of the vehicle of suspension carboxi-methyl cellulose (CMC) intraperitonially (i.p); ARS - (positive control) in which the animals received 100 mg L-1 arsenate and 0,5 mL of CMC/i.p; Vitamine E in which the animals received 100 mg L-1 arsenate and vitamin E/i.p (2mg in 0,5 mL of CMC); Guarana - in which the animals received 100 mg L-1 arsenate and guarana/i.p (2 mg g-1 of body weight in 0,5 mL of CMC); GUA / Vitamin E in which the animals received 100 mg L-1 and vitamin E (2mg in 0.5 mL of CMC) combined with guarana (2mg g-1 of body weight in 0.5 mL of CMC). The arsenate was supplied to the animals in drinking water and the treatments were administered in intervals of 72 h. After 42 days, which corresponds to a spermatogenic cycle, the animals under went euthanasia and subsequent analyses were done. The animals of the ARS group presented significant reduction in body, parhenquima and testicular weights, larger tecidual accumulation of arsenic and high concentrations of ALT, which suggests hepatotoxic action of the arsenate, besides a reduction in the volume of the seminiferous tubules, tubular diameter, in the proportion of the tunic own, height and proportion of the germinative epithelium and in the total daily spermatic production. In the intertubular compartment, increased proportion of volumetric of conjunctive tissue, macrophages and lymphatic space was observed, reduction in the proportion and volume of the cell of Leydig, nuclear diameter, nuclear volume, number of the cells of Leydig per testes and in the plasmatic concentration of testosterone. The sole administration of guaraná or guarana combined with vitamin E minimized most of the harmful effects of the arsenate in the structure and function of the male reproductive tract. Those data indicate the protective role of non-enzymatic compounds present in the diet such as vitamin E and guarana, which are capable of minimizing the effects of reactive species of oxygen. A exposição ao arsênio (As) pode ocorrer, principalmente, pela água de beber e, em algumas situações, por ingestão de alimentos contaminados, inalação e absorção cutânea. Processos naturais, industriais e antrópicos têm contribuído para aumentar os teores de As no meio. O As influencia a função reprodutiva masculina, afetando o processo espermatogênico, e várias evidências indicam sua ação tóxica está relacionado ao aumento da produção de espécies reativas de oxigênio. Estes efeitos deletérios podem ser minimizados pela administração de diversas substâncias, incluindo aminoácidos, vitaminas e compostos quelantes. O guaraná, planta originária da região amazônica, é rico em cafeína, flavonóides e taninos com propriedades antioxidantes, sendo utilizado na fitoterapia para a prevenção e o tratamento de doenças relacionadas ao desequilíbrio da atividade oxidante da célula. A vitamina E suprime a peroxidação lipídica no testículo e mitocôndrias, sendo capaz de reverter efeitos deletérios decorrentes da exposição testicular a diversos fatores como ozônio, ciclofosfamida, toxinas e contaminantes policlorados bifenilicos. O presente trabalho avaliou a capacidade do testículo e outras estruturas teciduais acumularem arsênio e os efeitos tóxicos decorrentes desse acúmulo, assim como o potencial antioxidante do guaraná e da vitamina E. Foram utilizados 35 camundongos Suíços com idade de 70 dias, divididos em cinco grupos contendo sete animais cada: CTR-(controle negativo) em que os animais receberam apenas água destilada e 0,5 mL do veículo de suspensão carboxi- metil celulose (CMC) via intraperitonial (i.p); ARS-(controle positivo) em que os animais receberam 100 mg L-1 de arsenato e 0,5 mL de CMC/i.p; VTE - em que os animais receberam 100 mg L-1 de arsenato e vitamina E/i.p (2mg em 0,5 mL de CMC); GUA- em que os animais receberam 100 mg L-1 de arsenato e guaraná/i.p (2 mg g-1 de peso corporal em 0,5 mL de CMC); GUA/VTE - em que os animais receberam 100 mg L-1 e vitamina E (2mg em 0.5 mL de CMC) associada ao guaraná (2mg g-1 de peso corporal em 0.5 mL de CMC). O arsenato foi fornecido aos animais na água de beber e os tratamentos administrados em intervalos de 72 h. Após 42 dias, o que corresponde a um ciclo espermatogênico, os animais sofreram eutanásia e procedeu-se às análises. Os animais do grupo ARS apresentaram redução significativa no peso corporal, peso do parênquima e peso testicular, maior acúmulo tecidual de arsênio e concentrações elevadas de ALT, o que sugere ação hepatotóxica do arsenato além de uma redução no volume dos túbulos seminíferos, diâmetro tubular, na proporção da túnica própria, altura e proporção do epitélio germinativo e na produção espermática diária total. No compartimento intertubular, observou-se aumento da proporção volumétrica de tecido conjuntivo, macrófagos, espaço linfático, redução na proporção e volume da célula de Leydig, diâmetro nuclear, volume nuclear número das células de Leydig por testículo e na concentração plasmática de testosterona. A administração isolada ou associada de guaraná e vitamina E minimizou a maioria dos efeitos deletérios do arsenato na estrutura e função do aparelho reprodutor masculino. Esses dados indicam papel protetor de compostos não-enzimáticos presentes na dieta, como a vitamina E e o guaraná, capazes de minimizar os efeitos de espécies reativas de oxigênio.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-05Bitstream added on 2014-06-13T19:01:36Z : No. of bitstreams: 1 machado_lp_dr_botfmvz.pdf: 310309 bytes, checksum: 5f3ffdabe328a78299d404b51f143e24 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) O objetivo deste trabalho foi avaliar os efeitos do exercício progressivo em esteira de alta velocidade, do treinamento e da suplementação com vitamina E no metabolismo do ferro e na lipoperoxidação eritrocitária em equinos Puro Sangue Árabe. Foram utilizados 16 animais, distribuídos em dois grupos: controle (GC=8) e suplementado com vitamina E (GE=8) (1.000 U/animal/dia). Os equinos não treinados foram submetidos a uma prova de exercício progressivo (P1). Em seguida, foram treinados por 20 dias e submetidos a uma segunda prova de exercício (P2). O protocolo de exercício para as duas provas iniciou-se a 1,8m/s por 5 min, 4m/s por 3min, 6m/s por 2min seguido de fases de 1min em velocidades crescentes até que os animais conseguissem manter-se em exercício, com a esteira inclinada a +7%. Não houve influência da suplementação com vitamina E ou do treinamento no metabolismo do ferro. O ferro sérico aumentou imediatamente após o exercício por hemoconcentração e houve redução por sequestro após 6h, retornando aos valores basais em 24h. O exercício induziu “pseudoanemia” entre 6 a 120h após o exercício nos animais não treinados. Não houve alteração na concentração de ferritina sérica. O MDA eritrocitário basal foi maior nos animais treinados e houve maior produção in vitro de MDA eritrocitário nos animais suplementados. O MDA sérico aumentou 30min após o exercício e a concentração de vitamina E sérica não se alterou. Conclui-se que este protocolo de exercício promove alteração da dinâmica de distribuição do ferro, mas não altera o conteúdo total de ferro do organismo. A mensuração do MDA sérico é sensível para avaliar o estresse oxidativo induzido pelo exercício, porém o MDA eritrocitário basal é mais eficiente para avaliar o estresse do treinamento. A suplementação com vitamina E não impediu o estresse oxidativo. This study aimed to evaluate the effects of incremental exercise in high-speed treadmill, training and vitamin E supplementation on iron metabolism and erythrocyte lipoperoxidation in Arabian horses. Sixteen animals were distributed into two groups: control (GC=8) and supplemented with vitamin E (GE=8) (1,000 U/animal/day). The untrained horses were submitted to an incremental exercise trial (P1). Then, they were submitted to a 20 day training period and to a second incremental exercise trial (P2). Exercise protocol for two tests was started with 1.8m/s for 5 min, 4m/s for 3 min, 6m/s for 2 min and right after, periods of 1 min and challenging the equines with increasing speeds until the animals hasn’t no condition to prolong the exercise. There was no influence of vitamin E supplementation or training on iron metabolism. Serum iron levels increased immediately after exercise due to hemoconcentration and there was a reduction by sequestration after 6 h, which returned to basal values in 24 h. The exercise induced a “pseudoanemia” 6 to 120 h after the exercise in untrained animals. There was no alteration in serum ferritin concentration. Basal erythrocyte MDA was higher in trained animals and there was major in vitro erythrocyte MDA production in supplemented animals. Serum MDA elevated 30 min after exercise and vitamin E concentration did not change. In conclusion, this exercise protocol promotes changes in iron distribution dynamic, but do not change the total iron containing in the organism. Serum MDA measurement is sensitive to evaluate the oxidative stress induced by exercise, however basal erythrocyte MDA is more efficient to evaluate training stress. Vitamin E supplementation not avoids oxidative stress.

Orientador: Wilma De Grava Kempinas Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: A hiperglicemia está relacionada com desordens no sistema reprodutor masculino. Quando induzida quimicamente, ela pode causar diminuição nos níveis dos hormônios sexuais, no peso dos órgãos reprodutores, na concentração espermática, na fertilidade bem como alteração no comportamento sexual de ratos machos. No homem, a hiperglicemia pode levar a impotência sexual, diminuição da libido e da espermatogênese. Contudo, os principais fatores que ocasionam essas alterações ainda são discutíveis. Uma das hipóteses seria o aumento do estresse oxidativo, o qual pode causar peroxidação lipídica nas membranas biológicas, neuropatias hiperglicêmicas, danificar a molécula de DNA e comprometer a comunicação celular. No entanto, há escassez de informações que relacionem o efeito do estresse oxidativo aumentado com a morfofisiologia do sistema reprodutor masculino em indivíduos hiperglicêmicos. Diante disso, o objetivo deste estudo foi avaliar se o tratamento com antioxidantes (vitaminas C e/ou E), ao diminuir o estresse oxidativo, poderia diminuir os danos causados pela hiperglicemia no sistema reprodutor masculino de ratos. Para tanto, a hiperglicemia foi induzida quimicamente utilizando dose única do antibiótico streptozotocin em ratos machos adultos (90 dias de idade; 9 ou 10/grupo experimental). Esses animais foram divididos em grupos experimentais que receberam vitamina C e E (sozinhas ou associadas), ou apenas os veículos (grupo normoglicêmico) durante trinta dias consecutivos por via oral. No 31º dia do período experimental, após a eutanásia dos animais, foi coletado sangue para avaliação dos biomarcadores do estresse oxidativo e dos níveis hormonais, e órgãos reprodutores para avaliação dos parâmetros espermáticos e resposta noradrenérgica do ducto deferente. O delineamento experimental acima descrito foi empregado a um outro lote de animais para realização das análises histopatológicas e morfométricas do testículo e epidídimo. Os resultados mostraram que a hiperglicemia causou significativo aumento do estresse oxidativo e da sensibilidade dos receptores a1 noradrenérgicos, diminuição no peso corporal e dos órgãos reprodutores, redução na motilidade espermática, no nível de testosterona, aumento no número de espermatozóides malformados e um rearranjo nos componentes do tecido epididimário. As vitaminas reduziram significativamente o nível do estresse oxidativo e o número de espermatozóides malformados, mas em ambos os casos a vitamina C foi mais efetiva. As vitaminas também reduziram parcialmente a sensibilidade dos receptores a à noradrenalina. Com relação aos prejuízos da motilidade espermática a vitamina C sozinha amenizou parcialmente essas alterações. Também, a administração da vitamina C sozinha preveniu a redução da proporção dos componentes epididimários. Além disso, a vitamina C sozinha e associada com a vitamina E restabeleceram parcialmente os níveis de testosterona. Entretanto, a associação das vitaminas causou uma redução significativa nos níveis de LH. Contudo, a produção espermática diária, o tempo de trânsito espermático pelo epidídimo, o aspecto histológico dos testículos e epidídimos, o diâmetro dos túbulos seminíferos, os níveis de FSH e a resposta máxima noradrenérgica foram estatisticamente semelhantes entre os grupos experimentais. Em conclusão, essas vitaminas, atuando como antioxidantes, podem diminuir algumas alterações no sistema reprodutor masculino de ratos causados pela hiperglicemia. Abstract: The hyperglycemia is related to disorders in the male reproductive system. When induced chemically, it can reduce the sexual hormones' level, reproductive organs' weight, sperm concentration, and fertility as well as the male rat sexual behavior. In men, the hyperglycemia can lead to sexual impotence, libido and spermatogenesis reduction. However, the main factors that are responsible for these alterations are still controversial. One of the possible causes for this would be the increase of the oxidative stress, which can cause lipid peroxidation in the biological membranes, hyperglycemic neuropathies, injury in the DNA molecule and to compromise the cellular communication. However, there is a lack of information related to the increased oxidative stress effect with the morphophysiology from the male reproductive system in hyperglycemic subjects. In this sense, the aim of the present study was to evaluate if the treatment with antioxidants (vitamins C and/or E), lowering the oxidative stress, could somehow attenuate the damages caused by hyperglycemia in the male rat reproductive system. Therefore the hyperglycemia was induced chemically using a single dose of streptozotocin antibiotic in male adult rats (90 days old; 9 or 10/experimental group). These animals were divided into experimental groups that received vitamin C or E (isolated or in association), or only the vehicles (normoglycemic group) during thirty consecutive days orally. At the 31st day from the experimental period, after the euthanasia of the rats, blood was collected to evaluate biomarkers of oxidative stress and hormonal levels, and reproductive organs to evaluate the permatic parameters and the noradrenergic response of vas deferens. The experimental design described above was applied in another amount of animals for the accomplishment of histopathological and morphometric analysis from testis and epididymis. The results showed that hyperglycemia caused significant increase in the oxidative stress and in the sensibility of noradrenergic a1 receptors, decrease in the body mass and in the reproductive organs' weights, reduction on the sperm motility, on epididymal tissue, in the testosterone level, an increase in the malformed sperm number and a rearrangement in the epididymal tissue components. The vitamins reduced significantly the level of oxidative stress and the number of malformed sperm, but in both cases vitamin C was more effective. These vitamins also reduced partly the sensibility to noradrenalin in the a receptors. In relation to the injuries in the sperm motility, the vitamin C alone attenuated partly these alterations. In addition, the vitamin C alone also prevented the reduction of the epididymal compartimental. Besides that, the vitamin C alone and in association to vitamin E reestablished partly the testosterone levels. Meanwhile, the association of the vitamins caused a significant reduction in the LH levels. Nonetheless, the daily sperm production, the transit time by epididymis, the histological aspect of the testes and epididymides, the seminiferous tubular diameter, the FSH levels and the maximum noradrenergic response were statistically equal among the groups. In summary, these vitamins, acting as antioxidants, may reduce some changes in the rat male reproductive system caused by hyperglycemia. Doutorado Biologia Celular Doutor em Biologia Celular e Estrutural

OBJETIVO: avaliar o nível de peroxidação lipídica e vitamina E no fluido folicular e soro de pacientes inférteis, com ou sem endometriose, submetidas à indução da ovulação para procedimentos de reprodução assistida. MÉTODOS: estudo prospectivo envolvendo, consecutivamente, 36 pacientes inférteis com idade entre 20 e 38 anos, divididas em dois grupos: Endometriose (n=17) e Controle (n=19, laqueadura tubária prévia ou fator masculino). Amostras sanguíneas foram coletadas em: D1 (imediatamente antes do início do uso de gonadotrofinas), D2 (dia da aplicação da gonadotrofina coriônica humana) e D3 (dia da aspiração folicular). Em D3, amostras de fluido folicular livres de contaminação sanguínea foram coletadas e armazenadas. O nível de eroxidação lipídica foi mensurado pela quantificação de malondialdeído (MDA) por espectrofotometria, e o status antioxidante por meio da medida da vitamina E por cromatografia líquida de alta pressão. RESULTADOS: em D1, nenhuma diferença significante foi observada entre os Grupos Endometriose (2,4 nmol/mL) e Controle (1,9 nmol/mL) no nível de MDA. Contudo, os níveis de vitamina E foram significativamente mais elevados no Grupo Controle (24 mimol/L). Em D2, os níveis de MDA foram significantemente maiores no Grupo Endometriose (2,3 nmol/mL) quando comparados com o Controle (1,4 nmol/mL), enquanto os níveis de vitamina E permaneceram significativamente mais elevados no Controle (23,4 mimol/L). Em D3 não houve diferença significante nos níveis de MDA e de vitamina E do soro e fluido folicular entre os grupos. Contudo, em D3, os níveis de vitamina E foram significativamente mais elevados no soro do que no fluido folicular em ambos os grupos, e os níveis de MDA foram significativamente menores no fluido folicular do que no soro apenas no Grupo Controle. CONCLUSÃO: antes do início da indução da ovulação, uma diminuição significativa nos níveis séricos de vitamina E foi observada em pacientes com endometriose, cujo consumo poderia estar contribuindo para a manutenção de níveis séricos de MDA similares ao Grupo Controle. Depois da indução da ovulação com gonadotrofinas exógenas, o grupo de pacientes com endometriose apresentou não somente aumento nos níveis séricos de MDA, mas também manteve status antioxidante inferior ao Grupo Controle. Contudo, no dia da captação oocitária, ambos os níveis séricos de MDA e de vitamina E foram semelhantes nos dois grupos. PURPOSE: to assess the level of lipid peroxidation (LP) and vitamin E in the follicular fluid and serum of infertile patients, with or without endometriosis, submitted to induction of ovulation for assisted reproduction procedures. METHODS: infertile patients aged 20 to 38 years old were selected prospectively and consecutively and divided into Endometriosis Group (17 patients with pelvic endometriosis) and Control Group (19 patients with previous tubal ligation or with male factor). Blood samples were collected on: D1 (before the beginning of the use of gonadotrophins), D2 (day of human chorionic gonadotrofin application) and D3 (day of oocyte retrieval). On D3, follicular fluid samples free from blood contamination were also collected and stored. LP was assessed for malondialdehyde (MDA) quantification by spectrophotometry, and antioxidant status by measurement of vitamin E by HLPC. RESULTS: on D1, no significant difference in LP was observed between groups. However, vitamin E levels were significantly higher in the Control Group. On D2, LP levels were significantly higher in the Endometriosis Group compared to Control and vitamin E levels continued to be significantly higher in the Control Group. On D3, there was no significant difference in both serum and follicular fluid levels of LP or vitamin E between groups. However, on D3, vitamin E levels were found to be significantly higher in serum than in follicular fluid in both groups, whereas MDA levels were significantly lower in follicular fluid than in serum only in the Control Group. CONCLUSION: before the beginning of the induction of ovulation, a significant decrease in antioxidant status was observed in patients with endometriosis, perhaps because antioxidants are consumed during oxidation reactions. After the induction of ovulation with exogenous gonadotrophins, the group of patients with endometriosis presented not only increased lipid peroxidation compared to Control, but also maintained a lower antioxidant status than the Control Group. However, on the day of oocyte retrieval, both serum LP potential and the levels of vitamin E were found to be similar in both groups.

Fil: González, Marcela Aída. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Hemos demostrado que el aluminio induce colestasis asociada a múltiples alteraciones en transportadores hepatocelulares que participan en la función secretora bibliar, al igual que Mrp2. El objetivo fue investigar si estos efectos perjudiciales son mediados por el estrés oxidativo causado por el metal. A tal efecto, fue estudiada la capacidad antioxidante de la vitamina E, en ratas Wistar macho. El aluminio se administró ip (27 mg / kg de peso corporal, tres veces a la semana, 90 días). Vitamina E (600 mg / kg de peso corporal) fue coadministrado, sc. El Aluminio aumento la peroxidación lipídica (+50%) y disminuyó el glutation hepático (-43%) y la actividad del glutation peroxidasa (-50%) y catalasa (-88%). La vitamina E contrarrestó total o parcialmente estos efectos. Los niveles de Al en plasma e hígado fueron significativamente reducidos por la vitamina E (-40% y -44%, respectivamente, p

La diarrea es una enfermedad con alta frecuencia en el mundo y es causa de mortalidad y desnutrición en los niños de países en desarrollo. Esto justifica el estudio de la alimentación durante la diarrea. Debido a las dificultades económicas y éticas del estudio de la diarrea infantil, es conveniente usar modelos de diarrea en animales. En estudios previos, se demostró que la diarrea inducida con lactosa en ratas, está asociada con una reducción de los niveles tisulares de vitamina E y también con evidencias de una respuesta inflamatoria a nivel intestinal. En consecuencia, en este estudio se produjo esta diarrea en ratas suficientes y deficientes en vitamina E, con el fin de establecer su efecto en los niveles de estrés oxidativo. Los resultados mostraron que en un lapso de 23 días la concentración de vitamina E tisular disminuyó en todas las ratas con diarrea, pero esta disminución fue sustancialmente mayor en las ratas deficientes en esta vitamina. Al mismo tiempo se observó que la severidad de la diarrea en las ratas deficientes en vitamina E fue un 60% mayor que en las ratas con diarrea pero suficientes en vitamina E. Tanto la diarrea como la deficiencia de vitamina E se asociaron con cambios en las concentraciones de malonaldehido y en la actividad de la superóxido dismutasa en varios tejidos. Sin embargo, los cambios más resaltantes asociados con la diarrea estuvieron relacionados a un aumento en los niveles plasmáticos de malonaldehido de casi 100% y una actividad de la superóxido dismutasa en los eritrocitos de las ratas con diarrea, que fue entre 8 y 11 veces mayor que la detectada en las ratas controles. Estos cambios no invasivos correlacionaron directamente con la severidad de la diarrea. El estudio muestra que la diarrea inducida con lactosa aumenta los niveles de estrés oxidativo y que la deficiencia de vitamina E se asocia con diarreas más severas. Diarrhea is the disease with high incidence in the world and causes infant mortality and malnutrition in the developing world. This justifies the study of nutrition and diarrhea. Due to ethical and financial considerations it is difficult to study nutrition and diarrhea in children thus animal models have become a convenient alternative. In previous studies it was shown that lactose induced diarrhea in rats was associated with a reduction in tissue levels of vitamin E and also with evidence of an inflammatory response of the intestine. Accordingly, in this study, in order to determine the effect of this type of diarrhea on the level of oxidative stress, diarrhea was induced in vitamin E sufficient and deficient rats. The results showed that after 23 days the tissue concentration of vitamin E decreased in all the rats with diarrhea but this reduction was substantially greater in the vitamin E deficient group. Moreover, diarrhea was 60% more severe in the vitamin E deficient rats than in the vitamin E sufficient group that also had diarrhea. Both diarrhea and vitamin E deficiency altered malonaldehyde and superoxide dismutase levels in various tissues. However, the most outstanding changes associated with diarrhea were a 100% increment in plasma malonaldehyde and erythrocyte superoxide dismutase activities which were 8 to 11 times higher than those seen in the rats without diarrhea. These non-invasive changes correlated well with the severity of diarrhea. The study shows that vitamin E deficiency results in diarrheas which are more severe and that lactose induced diarrhea is associated with higher levels of oxidative stress.