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Vallis, Katherine Anne. "Menadione resistance : a model for cellular defences against oxidative stress." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20853.
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To study the genetic changes which confer resistance to oxidants, cell lines that are resistant to the redox-cycling agent, menadione, have been isolated from Chinese hamster ovary (CHO) and human transitional carcinoma (EJ) parental cell lines. They exhibit cross-resistance to chemical oxidants (hydrogen peroxide and sodium arsenite) but not to ionising radiation (in oxic conditions). The concentrations of the major sources of intracellular thiol groups, glutathione and cysteine, are two-fold greater in menadione-resistant than in the corresponding parental cell lines. Exposure to menadione results in depletion of both glutathione and cysteine but the subsequent recovery of thiols is more rapid and of greater magnitude in menadione-resistant than sensitive cell lines. 1H spin echo nuclear magnetic resonance (NMR) spectroscopy was used to study intact cells. Using this technique the removal of menadione from suspensions of resistant and sensitive cells was observed. However, only in menadione-sensitive cells was concomitant depletion of the NMR-visible pool of glutathione observed. The acquisition of resistance to menadione was associated with significant changes in the expression of several enzymes that are implicated in the oxygen-induced stress response and in protection from redox-cycling agents. The transcription of genes encoding heme oxygenase and the glutathione-related enzymes, GST-Pi and glutathione peroxidase, increases in CHO parental cells after transient oxidative stress. These genes are constitutively induced in CHO menadione-resistant cell lines. This suggests that resistance results from perpetuation of a response that normally occurs only transiently.
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Hälldin, Jonas. "Oxidative stress and alterations in the mammalian iron metabolism : a study on iron, inflammation, oxidative stress and neurodegeneration in cellular model systems /." Stockholm : Department of Neurochemistry, Stockholm University, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7037.
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Crisóstomo, Luís Daniel Machado. "Pilot-model for oxidative post-competition recovery in swimmers." Master's thesis, Universidade da Beira Interior, 2013. http://hdl.handle.net/10400.6/1340.
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Physical exercise have several health benefits, but it can also be a source of cellular
damage. The energetic demands of physical exercise and training promote an increase on
metabolic rate, and its pathways may produce secondary harmful compounds that will cause
cellular damage. Some of those compounds are the free radicals and Reactive Oxygen
species, which are highly instable molecules that react quickly, oxidizing important functional
molecules such as proteins, membrane lipids and DNA, in a condition known as oxidative
stress. To dampen the action of these molecules, the cells express antioxidant defence
proteins. One of the most ubiquitous and polymorphic of those is the family of Gluthatione STransferases (GSTs). The great physical load of competitive training creates serious oxidative
stress on athletes so, it is expected that their expression of GSTs will vary throughout the
season to overcome such aggression, quickly recovering from one training session and
preparing the antioxidant defence for the next one.
Our main objective was to verify if the expression of a GST (GSTT1) varies throughout
the season, as expected theoretically, and how it fluctuates after a competition. We also
check if the distribution of the GSTM1 and GSTT1 Null/Present genotypes had some influence
in the preparation and performance of our sample, consisting in 20 national level swimmers.
A control group of 52 random individuals was also used to compare genotype distribution.
We collected blood samples in analytic filter paper, at 5 different moments
throughout the winter season. DNA was isolated from a sample of each individual, amplified
by PCR for our interest genes, and ran in agarose gel by electrophoresis to genotype our 20
swimmers. RNA was isolated from all the samples of a swimmer and converted in cDNA by
reverse transcriptase. The relative expression of GSTT1 was done using β-actin (a
housekeeping gene) as a control gene and the first collected sample of the swimmer as
control condition, by the RT-PCR technic. Three swimmers were accessed for the whole 5
moments, while eight were only evaluated their expression at 48h and 72h after competition.
The results showed little influence in the distribution of genotype from swimmers to
controls. The expression results show influence of the GSTT1 expression profile throughout
the season and after an intense exercise with sport performance and as a fitness check tool.O treino desportivo com o objetivo de performance competitiva coloca os atletas sob um forte risco de desequilíbrio oxidativo, conhecido por stress oxidativo. A produção de radicais livres e espécies electrofílicas, como as Espécies Reativas de Oxigénio (ROS), são uma constante no metabolismo normal do organismo, no entanto, a maior taxa metabólica exigida pela demanda energética do exercício físico intenso, provocam uma produção de tais espécies a um nível superior às defesas antioxidantes disponíveis. Nesta situação de stress oxidativo, os radicais livres e ROS provocam danos a fulcrais estruturas e macromoléculas celulares, reagindo forte e rapidamente com estas, ameaçando a homeostasia celular. Para controlar a ação nefasta dessas agressões oxidativas, os organismos possuem mecanismos de defesas antioxidantes, podendo estas ser de origem endógena ou exógena. Entre as defesas antioxidantes endógenas encontram-se proteínas expressas pelas células, e cuja expressão pode ser influenciada pelo ambiente oxidativo celular, como é o caso das Glutationa S-Transferases (GST). Desta forma, situações que criem stress oxidativo, como no treino desportivo, ativam a expressão das defesas antioxidantes. Assim sendo, o treino desportivo regular e bem planeado, de forma a evitar danos constantes ao organismo, deve ativar uma resposta deste de forma a protege-lo dessa agressão, preparando-o previamente para essa agressão. Essa preparação pode ser verificada através da expressão génica de fatores antioxidantes endógenos. Além disso, certos genótipos podem revelar-se vantajosos nesta proteção, nomeadamente os genótipos associados às várias isoformas das GSTs. Nestes, constam vários e frequentes genótipos Null (ausência do gene), o que permite uma grande variabilidade entre indivíduos para a disponibilidade de isoformas de GSTs. O objetivo deste trabalho foi precisamente verificar a distribuição de genótipos Null/Present para duas isoformas de GSTs, a GSTM1 e a GSTT1, numa amostra de 20 nadadores portugueses de nível nacional. Para comparação de genótipos, foi recolhida semelhante informação a partir de um grupo de controlo constituído por 52 indivíduos aleatórios. Além disso, observou-se a expressão relativa de GSTT1 ao longo de 5 momentos distintos ao longo da época de Inverno (preparação geral, preparação específica, fase taper e dois momentos pós-competição) em 3 desses atletas, e a expressão relativa, também de GSTT1, 48h e 72h após uma competição, para 8 desses atletas. Para conseguir alcançar isto, foi necessário montar uma técnica totalmente nova para recolher as amostras de forma rápida, fiável e praticável nas condições de treino, e otimizar todos os procedimentos laboratoriais para conseguir processar essas amostras de forma eficiente e rigorosa. As amostras foram recolhidas em papel de filtro de análises clínica, através de uma picada no dedo dos nadadores, antes do início do treino do dia definido previamente para recolha de amostras. As amostras foram ainda conservadas em invólucros individuais para cada recolha a cada momento e de cada atleta, numa câmara-fria 4°C, no Centro de Investigação em Ciências da Saúde (CICS) da Faculdade de Ciências da Saúde (FCS) da Universidade da Beira Interior (UBI). Para genotipagem dos nadadores em amostra, DNA foi extraído da amostra de sangue em papel utilizando o método do Chelex 100. Após extração, o DNA foi usado para amplificação enzimática da sequência específica dos genes da GSTM1 e GSTT1, pela técnica de PCR. Por fim, os resultados foram corridos por electroforese em gel de agarose, usando Green-safe como fator de marcação de DNA, e os resultados foram visualizados à luz ultravioleta num transiluminador. A presença de GSTM1 foi identificada pela presença de uma banda com cerca de 215bp, enquanto a presença de GSTT1 foi identificada pela presença de banda aos 473bp. Para análise da expressão génica, RNA foi isolado a partir das amostras de sangue em papel, pelo método do Trizol. O RNA era correspondente a cada um dos momentos de recolha. De seguida o RNA foi convertido a cDNA através da técnica de transcriptase reversa, utilizando a enzima M-MLV. Por fim, o cDNA foi amplificado pela técnica de RT-PCR, para o gene GSTT1, tendo ainda como controlo a amplificação da β-Actin, também para cada um dos momentos de recolha e fazendo duplicados por uma questão de rigor. A expressão foi calculada através das curvas de amplificação de RT-PCR e utilizando o método ΔΔCT. Não foram encontradas distribuições de genótipos GSTM1 e GSTT1 Null/Present estatisticamente significativas entre a nossa amostra de teste e o grupo de controlo. No contexto da expressão relativa de GSTT1, verificou-se que variações muito acentuadas ao longo da época desportiva ou após um exercício foram prejudiciais à performance física dos nadadores. Encontramos também algumas diferenças na recuperação das nadadoras, mantendo uma expressão mais alta e por um maior período de tempo após o exercício físico intenso que os homens. Além disso, verificou-se uma tendência para os indivíduos GSTM1 Null manterem os níveis de expressão relativa de GSTT1, ao longo da época e após um exercício intenso, mais estáveis, o que parece favorecer o seu rendimento. Conclui-se ainda que a análise da evolução da expressão relativa de GSTT1 em vários treinos, após uma competição ou outro exercício de elevada intensidade, pode ajudar a perceber qual a forma atual de um nadador.
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Hung, T. H. "In vitro hypoxia-reoxygenation as a model for placental oxidative stress in preeclampsia." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604788.
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Oxidative stress of the placenta is considered a key intermediary step in the pathogenesis of preeclampsia, but the cause for the stress remains unknown. Ischaemia-reperfusion injury, as a result of intermittent placental perfusion secondary to deficient trophoblast invasion of the endometrial arteries, is a possible mechanism. This thesis therefore tests whether hypoxia-reoxygenation (H/R) in vitro can induce placental oxidative stress, and cause increased apoptosis and production of tumour necrosis factor-α as seen in the preeclamptic placenta. The first aim was to examine the oxidative status of human placental tissues during periods of hypoxia and reoxygenation in vitro. Rapid generation of reactive oxygen species (ROS) was detected using a fluorescent marker when hypoxic villous samples were reoxygenated. The expression of oxidative stress markers including nitrotyrosine residues, 4-hydroxy-2-nonenal adducts, and inducible heat shock protein 72 was greatly increased in villous samples subjected to H/R compared to the controls maintained under constant hypoxia. Furthermore, preloading villous samples with ROS scavengers such as desferrioxamine and α-phenyl-N-tert-butylnitrone significantly reduced the levels of oxidative stress in H/R. Having demonstrated that in vitro H/R is capable of inducing oxidative stress in a reproducible and manipulable manner, investigations were next carried out to study the effects of resultant oxidative stress on apoptosis within the trophoblast. Compared to hypoxic and normoxic controls, there was a significant increase in the release of cytochrome c from mitochondria, activation of caspase , and cleavage of poly (ADP-ribose) polymerase in villous samples subjected to H/R. These events were associated with an increased number of syncytiotrophoblastic nuclei displaying apoptotic changes and increased lactate dehydrogenase release into the medium. The causal relationship between the generation of ROS and these apoptotic changes was revealed by the fact that pre-administration of desferrioxamine attenuated the insult.
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Millican, Stephanie A. "Human vascular endothelial cells in culture : a model system for studying oxidative stress." Thesis, University of Aberdeen, 1993. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU554288.
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Cell culture systems were used to investigate the mechanisms of oxidant-induced cellular damage. The Girardi heart cell line was used to investigate possible mechanisms of ischaemic cell damage whilst human endothelial cells derived from the umbilical vein (HUVEC) were used to study the direct cellular effects of hydrogen peroxide (H2O2). A number of parameters including cytosolic enzyme leakage, ATP content and DNA and protein synthesis were used to assess cell damage. Girardi cells were found to be resistant to the effects of oxygen deprivation. In contrast, HUVEC were sensitive to H2O2 and concentrations of H2O2 250M resulted in irreversible cell damage. Irreversible damage produced by H2O2 was dependent upon the initial exposure time of the cells to H2O2, the cellular metabolism of H2O2 and the possible conversion of H2O2 to the hydroxyl radical via the iron catalysed Fenton reaction. Catalase activity was not detectable in HUVEC. In contrast, HUVEC contained relatively high concentrations of reduced glutathione (GSH) which decreased, with growth, during culture and were also reduced by the experimental treatment conditions. Cell damage appeared to occur independently of cellular GSH, however depletion of GSH with butathione sulfoximine, to below 10&'37 of control values did potentiate cytotoxicity in response to H2O2. Depletion of ATP, alone, did not correlate with irreversible cell damage. However, cells could recover from oxidant damage as long as the capability to synthesise ATP was maintained. The main mechanism by which ATP was depleted was via the activation of poly (ADP-ribose)polymerase, as demonstrated by the ability of 3-Aminobenzamide to prevent ATP depletion and cell lysis. The mechanism for this activation is most likely to be a consequence of hydroxyl radical-induced damage to DNA. However, activation of poly(ADP-ribose)polymerase was not the only mechanism which accounted for the depletion of ATP and a H2O2-dependent pathway appeared to exist.
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Zhong, Wenwen. "Protection against oxidative stress in human endothelial cells in an in vitro diabetes model." Thesis, University of Hull, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431079.
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Duggan, Simon. "The role of mitochondria and oxidative stress in a model of coronary artery disease." Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.761669.
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Alinde, Olatogni Berenice Lidwine. "Effects of red palm oil-supplementation on oxidative stress biomarkers in an experimental rat model." Thesis, Cape Peninsula University of Technology, 2012. http://hdl.handle.net/20.500.11838/2257.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2012.Oxidative stress, in recent times appears to be a major underlying risk factor in the occurrence of various diseases such as cardiovascular disease (CVD) and ischemic heart disease (IHD). During oxidative stress, there is an imbalance between the production of reactive oxygen species (ROS) and antioxidant defence mechanisms in favour of ROS. This results in severe cellular damages in the heart, vascular membranes and other organs. Potential benefits of dietary supplements as one of the major quenching elements against oxidative stress have been highlighted. Thus, a growing interest has been stimulated in finding natural alternatives for the treatment and! or prevention of oxidative stress-mediated diseases. Red palm oil (RPO), refined from the tropical plant Elaeis guineensis was used in this study since it has captivated much attention in the health sector lately. The effects of RPO-supplementation on oxidative stress biomarkers as well as homocysteine, a cardiovascular disease risk factor in an oxidative stress-induced rat model were investigated in this in vivo study. All experiments were conducted for a period of six weeks. Male Wistar rats (120-150g) were randomly divided into six groups (n=5) where all the rats received a standard diet. Two groups (groups C, D) were supplemented with 0.175g RPO (7g RPO/kg chow) for four weeks whereas groups (groups E, F) were given 0.175g RPO (7g RPO/kg chow) supplementation for six weeks. Rats in control groups (groups A, B) were not given any RPO-supplementation. Groups B, 0, F were induced with oxidative stress by injection of 0.5ml (20IlM/100g of body weight) organic tertiary-butyl hydroperoxide. All parameters were determined using appropriate methods in plasma, serum and erythrocytes. Data were expressed as mean ± SEM. No significant differences were obtained between groups for total antioxidant capacity and glutathione peroxidase activity. Red palm oil supplementation significantly increased superoxide dismutase activity after 6 weeks consumption, total glutathione levels after 4 weeks consumption and homocysteine levels after four and six weeks consumption in rats not subjected to oxidative stress. Under oxidative stress conditions, malondialdehyde (MOA) level, a marker of oxidative stress related damage, significantly increased in rats receiving a standard diet. However, when RPO diet was supplemented for 4 and 6 weeks, MOA levels significantly decreased towards the value of normal controls. In conclusion, our findings suggest that RPO-supplementation could ameliorate antioxidant status in the body through its potential ability to increase some antioxidant enzymes activity. Similarly, it is suggested that RPO-supplementation could protect the rat against oxidative stress induced damage in diseased state.
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Miller, Rebecca Louise. "The mechanism for paraquat toxicity involves oxidative stress and inflammation a model for Parkinson's disease /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4764.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2007" Includes bibliographical references.
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Du, Plessis Michelle. "The role of carnitine in eukaryotic cells : Using yeast as a model." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97946.
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Thesis (MSc)--Stellenbosch University, 2015.ENGLISH ABSTRACT: Previous studies in yeast in this laboratory have found carnitine to be both protective against oxidative stress induced by hydrogen peroxide and to increase the detrimental effect of dithiothreitol. These phenotypes were found to be independent of the role of carnitine within the carnitine shuttle. A screen for suppressor mutations for these carnitine-dependent phenotypes identified, among others, Δcho2 and Δopi3. Cho2p and Opi3p catalyse the sequential methylation reactions in the formation of phosphatidylcholine from phosphatidylethanolamine. Therefore, this study aimed to investigate the relationship between choline, phosphatidylcholine and the carnitine phenotypes. Liquid growth assays of Δcho2 and Δopi3 cultures revealed that addition of choline can restore the protective effects of carnitine against hydrogen peroxide. The connection between the cellular phospholipid composition and the carnitine-dependent shuttleindependent phenotypes was also investigated. Analysis of the lipid composition of cells by LCMS showed that Δcho2 and Δopi3 had a largely different lipid composition compared with the wild type, most notably, a reduction in phosphatidylcholine and an increase in triacylglycerol content were observed for both mutants. These changes were reversed by supplementation with choline. However, no effects on the lipid composition of cells in response to carnitine treatment were observed, either when supplemented alone or in combination with DTT and hydrogen peroxide. Carnitine has also been investigated in mammalian systems for its potential to protect cells from oxidative stress, an effect which would be of benefit in various neurodegenerative disorders. Several studies have documented the positive effects of carnitine against oxidative stress in mammalian cells however the mechanism behind this action remains unknown. It is therefore thought that, provided similar effects for carnitine can be shown in mammalian cells as was observed in yeast, it would be beneficial to use yeast as a model system for the study of the molecular changes induced by carnitine. In view of this, the effects of carnitine on toxicity induced by oxidative stress in mammalian neural cells were compared to that which has been observed in yeast. For this purpose the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, a measure of reductive capacity of cells, was used. However, no effects for carnitine were observed in the MTT assay in combination with either dithiothreitol or paraquat.
AFRIKAANSE OPSOMMING: Vorige studies op gis in hierdie laboratorium het bevind dat karnitien beskermend is teenoor oksidatiewe stres wat deur waterstofperoksied geïnduseer word en ook die nadelige effek van ditiotreitol verhoog. Hierdie fenotipes is gevind om onafhanklik te wees van die rol van karnitien binne die karnitien-pendel. Die sifting vir onderdrukker-mutasies van hierdie karnitienafhanklike fenotipes het onder andere Δcho2 en Δopi3 geïdentifiseer. Cho2p en Opi3p kataliseer die opvolgende metileringsreaksies tydens die vorming van fosfatidielcholien vanaf fosfatidieletanolamien. Hierdie studie het dus gepoog om die verhouding tussen cholien, fosfatidielcholien en die karnitienfenotipes te ondersoek. Vloeistofanalises van Δcho2- en Δopi3-kulture het aangedui dat die byvoeging van cholien die beskermende effekte van karnitien teenoor waterstofperoksied kan herstel. Die verband tussen die sellulêre fosfolipiedsamestelling en die karnitienafhanklike pendel-onafhanklike fenotipes is ook ondersoek. Die analise van die lipiedsamestelling van selle deur middel van LCMS het getoon dat Δcho2 en Δopi3 ‘n grootliks verskillende samestelling het in vergelyking met die wilde tipe, en daar is veral ‘n afname in fosfatidielcholien en ‘n verhoging in triasielgliserol-inhoud vir beide mutante waargeneem. Hierdie veranderinge is omgekeer deur aanvulling met cholien. Geen effekte op die lipiedsamestelling van die selle is egter in reaksie op die karnitienbehandelings waargeneem nie, hetsy toe dit alleen aangevul is of in kombinasie met ditiotreitol en waterstofperoksied. Karnitien is ook in soogdierstelsels ondersoek vir sy potensiaal om selle teen oksidatiewe stres te beskerm, ‘n effek wat groot voordeel sal inhou vir verskeie neurodegeneratiewe steurings. Verskeie studies het reeds die positiewe effekte van karnitien teen oksidatiewe stres in soogdierselle opgeteken, hoewel die meganisme agter hierdie werking nog onbekend is. Daar word dus vermoed dat, gegewe dat soortgelyke effekte vir karnitien in soogdierselle getoon kan word as wat in gis waargeneem is, dit voordelig sou wees om gis as ‘n modelsisteem vir die studie van die molekulêre veranderinge wat deur karnitien geïnduseer word, te gebruik. In die lig hiervan is die effekte van karnitien op giftigheid wat deur oksidatiewe stres in soogdiersenuselle geïnduseer is, vergelyk met dít wat in gis waargeneem is. Om hierdie rede is die 3-[4,5-dimetieltiasool-2-iel]-2,5-difeniel tetrasoliumbromied (MTT) essaiëring, ‘n meting van die verminderende kapasiteit van selle, gebruik. Geen effekte vir karnitien is egter met die MTT essaiëring in kombinasie met óf ditiotreitol óf parakwat waargeneem nie.
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Alonis, Melenie Lee. "Selenotrisulfide Derivative of Alpha-Lipoic acid: Evaluation in a Cell Culture Model for Potential Use as a Topical Antioxidant." Master's thesis, University of Central Florida, 2005. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3451.
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Selenium is a required micronutrient in mammalian cells. It is incorporated in the form of selenocysteine into selenoenzymes such as glutathione peroxidase and thioredoxin reductase, and is absolutely required for activity. Thioredoxin reductase is necessary for reduction of oxidized thioredoxin and therefore plays a major role in maintaining the redox status of the cell. Glutathione peroxidase is responsible for reducing peroxides into their corresponding alcohols and water. Together, these selenoenzymes constitute a significant part of the cell's arsenal to defend itself against oxidative stress. Exogenous sources of oxidative stress, such as UV radiation, are capable of generating reactive oxygen species (ROS). Elevated levels of ROS can lead to covalent modifications of lipids, nucleic acids, and proteins within a cell. This damage has been implicated in the development of cancer and degenerative diseases. As the skin is the first level of defense for UV radiation, skin cancer is an obvious concern. Previous studies have demonstrated a protective effect against UV-induced cytotoxicity when selenium compounds were administered to skin cells in cell culture models. Topical selenium application to mice has also been shown to reduce UV damage to skin. Although a variety of chemical forms of selenium are available in nutritional supplements, the efficiency by which they are used for selenoprotein synthesis varies greatly. It is debated within the selenium research community which form is best for use as a supplement. In this study, we have focused on a selenotrisulfide derivative of alpha-lipoic acid (LASe). We have examined its utilization for selenoprotein synthesis through radiolabeling studies (75Se) in a human keratinocyte cell line (HaCaT). We have determined that is incorporated into selenoproteins with nearly the same efficiency as selenite and L-selenocysteine. We have also determined that LASe is far more efficient as a supplement in cell culture than selenate or L-selenomethionine, two forms of selenium commonly used as supplements. LASe was also found to protect HaCaT keratinocytes from UV- induced cytotoxicity. Cells pretreated with LASe and exposed to 500J/m2 and 750J/m2 of broadband (UVA/UVB) UV radiation showed greater survival than untreated controls in a dose –dependent manner. Cells pre-treated either with lipoic acid or selenium in the form of selenite alone also observed protection. Nonetheless, these finding are significant given that LASe was previously shown to penetrate the skin better than other forms of selenium. These results indicate that LASe has the potential for use as a topical antioxidant upon further testing in animal studies.M.S.
Department of Molecular Biology and Microbiology
Burnett College of Biomedical Sciences
Molecular Biology and Microbiology
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Maskiny, Charbel Farid. "Inflammatory Response and Oxidative Stress in Rats Selected for Intrinsic Aerobic Endurance Capacity." University of Toledo Health Science Campus / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=mco1180467082.
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Kamalvand, Golnar. "Evidence of oxidative stress response in a mouse model of AA amyloidosis : immunolocalization of specific markers." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80297.
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Amyloidosis describes a heterogenous collection of systemic diseases characterized by the extracellular deposition of proteinaceous amyloid fibrils derived from normally soluble proteins. With progressive tissue deposition of amyloid, death can occur through failure of the affected organ(s). However, the mechanism of amyloid fibril formation remains obscure. To understand this mechanism, a parasite (alveolar hydatid cyst, AHC)-mouse model of inflammation-associated AA amyloidosis, was used. AHC is a potent inducer of chronic inflammation, serum amyloid A (SAA) synthesis and AA amyloidosis. It has been proposed that reactive oxygen radicals (ROR) generated by inflammatory macrophages (mphi) and reticuloendothelial (RE) cells, which are also intimately involved in SAA clearance, could initiate intra-lysosomal AA fibril formation. ROS generated intracellularly could oxidize SAA fragments or other key cellular proteins, alter them structurally and thus render them resistant to enzymatic degradation and prone to intralysosomal nascent AA fibril formation.The objective of this research was to identify oxidative stress (OS) markers (heme-oxygenase-1, HO-1; 4-hydroxy-2-nonenal, HNE; Nepsilon -(Carboxymethyl)lysine, CML) in peritoneal mphi and splenic/hepatic RE cells obtained from AHC-infected mice prior to and during AA amyloidosis. Histochemical and peroxidase-immunoperoxidase methods were used to detect the OS markers. High levels of HO-1, an antioxidant enzyme; HNE, a product of lipid peroxidation; and CML, an advanced glycation end product, were found in peritoneal mphi and splenic/hepatic RE cells proximal to AA fibril deposition. HNE and CML deposits were found in both the tissue interstitium and bound to AA amyloid deposits, indicating their possible role in the oxidative alteration of intracellular SAA. OS mediated changes in mphi/RE cells loaded with SAA may prove to be a prelude to nascent intracellular AA fibril formation.
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Liu, Beinan. "Iron mediated amyloid beta toxicity and oxidative stress in a Drosophila melanogaster model of Alzheimer's disease." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608978.
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Fu, Zhongjie, and 傅中捷. "Effect of aldose reductase in an animal model of oxygen-induced retinopathy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47869392.
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Retinopathy of prematurity (ROP) commonly occurs in premature babies, with the first phase of vessel cessation followed by a second phase of vessel proliferation. In addition to vascular changes, neuronal abnormalities have also been observed. However, evidence for morphological changes of retinal neurons at the cellular level is lacking.
Oxidative stress has been highly indicated in the pathogenesis of ROP. Increased oxidative stress level was demonstrated in preterm babies expecially in those with ROP. The activity of aldose reductase (AR), the first enzyme in the polyol pathway, has been found to contribute to oxidative stress. Therefore, the role of AR in ROP was examined using a mouse model of oxygen-induced retinopathy (OIR), which was a well-established model to mimic human ROP.
Studies in examining the effects of AR on retinal vasculature showed that genetic deletion or pharmacological inhibition of AR reduced vaso-obliteration and neovascularization, possibly through regulating VEGF-induced pathway. In addition, morphological changes of various retinal neurons at different time points in the mouse model of OIR were also demonstrated. The degree of effects from hyperoxic and hypoxic exposure appeared to depend on the different stages of maturation of various retinal neurons. AR deficiency showed protective effects on retinal neurons including horizontal cells, rod bipolar cells and amacrine cells, possibly through attenuating the damage on blood vessels as well as facilitating blood vessel re-growth in the avascular area which provide more nutrients and supply to the retinal neurons.
To elucidate the protective role of AR deficiency in ROP, the changes in oxidative stress and oxygen-dependent gene expression including HIF-1α and iNOS were investigated. AR deficiency attenuated oxidative stress induction to protect the neonatal retina. In addition, AR deficiency also showed attenuated HIF-1α expression and enhanced iNOS expression. This served to strictly control the HIF-1α level which in turn can tightly regulate VEGF induction in the mouse retinae after OIR.
In order to further elucidate the role of AR in the pathogenesis of ROP, effects of AR deficiency on glial cells and microglia were investigated. AR deficiency reduced retinal astrocytic activation in hyperoxia and induced early M?ller cell gliosis in hypoxia. In addition, AR deficiency enhanced the specific function of microglia in different areas with facilitation of revascularization in avascular area and promotion of tufts regression in neovascular area. Moreover, AR deficiency also reduced the activation of a key inflammatory mediator NF-κB, which was considered to contribute to neovascularization. Therefore, AR deficiency demonstrated regulatory roles in reponses of glial cells, microglia and inflammation, contributing to the protective effects on neonatal retina in the mouse model of OIR.
Taken together, AR deficiency reduced the vascular and neuronal changes possibly through attenuating oxidative stress and glial responses as well as modulating inflammatory responses, indicating a beneficial role of AR inhibition in OIR. These findings highly suggest the therapeutic potential of AR inhibition in the treatment of ROP.published_or_final_version
Anatomy
Doctoral
Doctor of Philosophy
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Wilson, Malinda. "Drosophila melanogaster as a model organism for understanding the interrelationship of micronutrient antioxidants and atmospheric oxidative stress /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.
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Williams, Alison Suzanne. "Mechanisms of Oxidative stress induced airways hyperresponsiveness and lung neutrophillia in a murine model of ozone exposure." Thesis, Imperial College London, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498241.
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Lockman, Khalida Ann. "The relationship between oxidative stress, triglyceride accumulation and mitochondrial function in in vitro model of hepatocellular steatosis." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/24849.
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There is still debate about the relationship between fat accumulation and mitochondrial function in nonalcoholic fatty liver disease. It is a critical question since a proportion of individuals with steatosis progress to steatohepatitis. This thesis is focused on defining i) the effect of triglyceride accumulation and reactive oxygen species (ROS) on mitochondrial function ii) the contribution of triglyceride, ROS and subsequent mitochondrial impairment to the metabolism of energy substrates iii) the effect of the intracellular antioxidant, N-acetylcysteine, on hepatic mitochondrial function and metabolic alterations associated with human steatohepatitis iv) the effect of different free fatty acids species on ROS production and subsequent metabolic response in hepatocytes. To address these questions, we designed in vitro models using human hepatoblastoma C3A cells treated with various combinations of oleate, octanoate (O), lactate (L), pyruvate (P) and ammonia (N) acutely or for 72 hours, before measurements of triglyceride concentration, cell respiration, ROS production, mitochondrial membrane potential, ketogenesis and gluconeogenesis, metabolomics analyses, confocal and electron microscopy. Acutely, LPON treatment enhanced mitochondrial respiration and ROS formation. After 72 hours, despite the similarities in triglyceride accumulation, LPON treatment, but not oleate, dramatically affected mitochondrial function as evidenced by decreased respiration, increased mitochondrial membrane potential and enhanced ketogenesis. Importantly, this was associated with increased markers of oxidative stress and enhanced gluconeogenesis. Furthermore, reduction in triglyceride with metformin did not improve mitochondrial function. By comparison, respiration and ROS formation remained unperturbed with oleate. The addition of the antioxidant N-acetylcysteine prevented mitochondrial dysfunction and reversed metabolic changes seen with LPON, strongly suggesting ROS involvement in mediating mitochondrial impairment. Our data indicate that increased ROS formation, rather than cellular steatosis per se, impairs mitochondrial function. Thus, reduction in cellular steatosis may not always be the desired outcome without concomitant improvement in mitochondrial function and/or a decrease in ROS formation.
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Terpstra, Brian T. "Purine Nucleoside Mediated Neuroprotection in the 6-Hydroxydopamine Rodent Model of Parkinson's Disease." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298395215.
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Colbert, Kathryn Eileen. "Influence of dietary starches differing in glycemic index on pro-oxidant and anti-oxidant gene expression and insulin sensitivity in a mouse model." Auburn, Ala., 2007. http://repo.lib.auburn.edu/07M%20Theses/COLBERT_KATHRYN_13.pdf.
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Wanjiku, Samuel Mburu. "Impact of inflammation-induced oxidative stress on the integrity of immuno-haematopoietic cells and potential ameliorating interventions in an in vitro HIV model." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/95467.
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Thesis (PhD)--Stellenbosch University, 2013.ENGLISH ABSTRACT: Chronic inflammation and immune activation are hallmarks of HIV infection, resulting in chronic oxidative stress with over-utilization of antioxidant defences, which may contribute to the loss of immune cells and faster disease progression. Low levels of antioxidants in HIV- infected individuals have been associated with frequent opportunistic infections and an increased risk of mortality. HIV infection is also associated with on-going and aberrant activation of both the innate and adaptive immune systems. An important aspect of innate immune stimulation is derived from the leakage of lipopolysaccharide (LPS) across the damaged mucosal lining of the gut in early HIV infection. The impact of this innate immune stimulation on the adaptive arm of the immune system, as represented in this study by levels of CD4+ T-cell activation and death, have not been explored previously in untreated HIV infection. Using an integrated approach of immune activation, inflammation, oxidative stress and ameliorating antioxidant intervention for the first time, this thesis reports the impact of inflammatory induced-oxidative stress on CD4+ T-cells in an in vitro HIV model. In a preliminary study, baseline levels of neutrophil respiratory burst as an in vitro indication of immune stimulation were investigated. The relationships between baseline total antioxidant status (TAS), Red blood cell (RBC) antioxidant enzyme activities (catalase, superoxide dismutase & glutathione peroxidase), lipid peroxidation and glutathione redox ratio and other markers of disease in asymptomatic, untreated HIV infection were also explored. The design and optimization of an assay that could determine the effects of LPS-induced oxidative stress on CD4+ T-cells, was a critical part of this study. The development of this assay enabled the measurement of the effects of selected antioxidant interventions N-acetyl cysteine (NAC) and vitamin C, on LPS-induced CD4+ T-cell activation and death. The results were also correlated with CD4 count, viral load and markers of inflammation (fibrinogen & D-dimers) in HIV-infected and uninfected groups. Neutrophils from HIV-infected persons at rest showed a ―primed‖ response to low stimulating agent, bacterial N-formyl peptides (fMLP), which was significantly (P = 0.04) higher than uninfected individuals. There was increased oxidative stress as evidenced by increased catalase activity, malondialdehyde (MDA) and conjugated dienes (CDs) with a corresponding decrease in antioxidant capacity in HIV-infected individuals with lower CD4 count. NAC in combination with vitamin C, significantly (P = 0.0018) reduced activation of CD4+ T-cells to a greater degree than with either antioxidant alone. NAC and vitamin C individually and in combination significantly (P = 0.05, P = 0.012 and P<0.0001) decreased the expression of the markers of apoptosis, Annexin V and 7-amino-actinomycin (7-AAD). Importantly, the antioxidant combination decreased MDA values and significantly (P = 0.01) increased the glutathione redox ratio in the HIV-infected group. Based on these results, the respiratory burst and LPS-induced activation may be important contributing factors in inflammatory-associated oxidative stress in HIV infection and contribute to the depletion of CD4+ T-cells in the asymptomatic stage of HIV infection. These results also indicate the potential inhibitory effects of NAC and vitamin C in combination as agents that may limit immune activation and inflammation-induced oxidative stress. Importantly, the study showed that at this asymptomatic stage, CD4+ T-cells of the HIV-infected group responded similarly to stimulation as the HIV negative group, indicating that antioxidant defences were still functional and that appropriate early intervention at this stage may be protective against oxidative damage to the immune cells. To the best of our knowledge, this study is the first to use an integrated approach involving not only plasma levels of antioxidant status, but also RBC antioxidant enzyme activities, oxidative damage (lipid peroxidation), inflammation, cellular levels of immune activation and potential ameliorating interventions in evaluating the problem of inflammation-induced oxidative stress in HIV infection. Based on the results of this study, it is envisaged that an insight into the immune activation, inflammatory and oxidative stress status of patients will enable long-term profiling of each patient with a view to individualized therapy. This approach may have a direct impact on patient care in resource-limited settings such as sub-Saharan Africa.
AFRIKAANSE OPSOMMING: Chroniese inflammasie en immuunaktivering is kenmerke van MIV-infeksie. Dié twee prosesse lei tot chroniese oksidatiewe stres en oorbenutting van antioksidant verdedigingstelsels, wat lei tot die verlies van die immuun selle en vinniger siektevordering. Lae vlakke van antioksidante in MIV-positiewe individue stem ooreen met gereelde opportunistiese infeksies en 'n verhoogde risiko van mortaliteit. MIV-infeksie word ook geassosieer met langdurige en abnormale aktivering van beide die ingebore en aanpasbare immuunstelsels. 'n Belangrike aspek van ingebore immuun stimulasie in die raamwerk van vroeë MIV-infeksie, is die lekkasie van LPS oor die beskadigde slymvlies voering van die dunderm. Die impak van die ingebore immuun stimulasie op die aanpasbare arm van die immuunstelsel, soos aangetoon in hierdie studie deur die vlakke van CD4 T-sel aktivering en apoptose, is nog nie voorheen ondersoek in onbehandelde MIV-infeksie nie. Met behulp van 'n oorspronklike, geïntegreerde benadering van immuun aktivering, inflammasie, oksidatiewe stres en 'n lae vlak van antioksidant intervensie, lewer hierdie tesis verslag oor 'n in vitro model van inflammasie-geïnduseerde oksidatiewe stres op CD4 T-selle. In 'n voorlopige studie, is basislyn vlakke van die neutrofiel respiratoriese uitbarsting as 'n in vitro aanduiding van immuunstimulasie ondersoek. Die verhoudinge tussen basislyn totale antioksidant status (TAS), rooi bloed sel (RBC) antioksidant ensiemaktiwiteit (katalase, superoksied dismutase, en glutatioon peroksidase), lipied peroksidasie en glutatioon redoks-verhouding, asook ander merkers van siektevordering in asimptomatiese, onbehandelde MIV-infeksie is ook ondersoek. Die ontwerp en optimisering van 'n toets wat die effek van LPS-geïnduseerde oksidatiewe stres op CD4 T-selle kan bepaal, was 'n kritieke deel van hierdie studie. Die ontwikkeling van hierdie toets het ook die meting van die effek van toevoeging van twee geselekteerde anti-oksidante, N-asetiel sisteïen (NAC) en vitamien C, op LPS-geïnduseerde CD4 T-sel aktivering en apoptose ondersoek. Die resultate is ook gekorreleer met CD4-telling, virale lading en merkers van inflammasie (fibrinogeen en D-dimere) in groepe met en sonder MIV-infeksie. Neutrofiele van asimptomatiese persone met MIV infeksie, het 'n 'voorbereide' reaksie gehad teen ‗n lae stimulerende agent, bakteriële N-formiel peptied (fMLP), wat beduidend (P = 0,04) hoër was as in individue sonder MIV infeksie. Daar was verhoogde oksidatiewe stres soos bewys deur verhoogde katalase aktiwiteit, malondialdehied (MDA) en gekonjugeerde diëne (CDs), saam met 'n ooreenstemmende afname in anti-oksidant kapasiteit in MIV-positiewe individue met laer CD4-tellings. NAC in kombinasie met vitamien C, het die aktivering van CD4 T-selle beduidend verminder (P = 0,0018), 'n effek wat groter was in vergelyking met elke antioksidant alleen. NAC en vitamien C alleen, en in kombinasie het beduidend die uitdrukking van die merkers van apoptose, Annexin V en 7-AAD verminder (P = 0,05, P = 0.012 en P<0,0001). Wat belangrik is, is dat die afname in MDA waardes as gevolg van antioksidante in kombinasie, 'n beduidende styging in die glutatioon redoks verhouding in die MIV-positiewe groep tot gevolg gehad het. Hierdie resultate het aangetoon dat die respiratoriese uitbarsting en LPS-geïnduseerde aktivering belangrike bydraende faktore mag wees in inflammasie-verwante oksidatiewe stres in MIV-infeksie, wat kan bydra tot die uitputting van CD4 T-selle in die asimptomatiese stadium van MIV-infeksie. Hierdie resultate dui ook aan dat die moontlike inhiberende effekte van NAC en vitamien C in kombinasie, immuun aktivering en geïnduseerde oksidatiewe stres kan beperk. Van belang is die feit dat hierdie studie bewys het dat in die asimptomatiese stadium van MIV-infeksie, CD4 T-selle weens stimulasie dieselfde gereageer het as dié van mense sonder MIV infeksie. Dit het aangedui dat antioksidant verdediging in hierdie stadium nog funksioneel was, en dat 'n toepaslike vroeë intervensie op hierdie stadium beskermend teen immuun-sel oksidatiewe skade kan wees. Tot die beste van ons kennis, is hierdie studie die eerste om 'n geïntegreerde benadering te gebruik, waar plasma vlakke van antioksidant status saam met RBC antioksidant ensiemaktiwiteit, oksidatiewe skade (lipied peroksiidasie), inflammasie, sellulêre vlakke van immuunaktivering, en potensiële beskermende ingrypings ondersoek is in die evaluering van die probleem van oksidatiewe stres in MIV-infeksie wat tot inflammasie lei. Gebaseer op dié resultate, word dit in die vooruitsig gestel dat 'n insig in die status van immuunaktivering, inflammasie, en oksidatiewe stress van pasiënte, dit moontlik sal maak vir langtermyn- beplanning om vir elke pasiënt individuele terapie voor te skryf. Hierdie benadering kan 'n direkte impak op die sorg van pasiënte in hulpbron-beperkte gebiede soos sub-Sahara Afrika hê.
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Wiedenheft, Blake Alan. "Sulfolobus as a model organism for the study of diverse biological interests forays into thermal virology and oxidative stress /." Diss., Montana State University, 2006. http://etd.lib.montana.edu/etd/2006/wiedenheft/WiedenheftB1206.pdf.
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Bi, Chongshan. "The role of caveolin-1 phosphorylation in AQP4 membrane expression in a model of oxidative stress in primary astrocyte cultures." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/37065.
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Astrocytes play an important role in a wide variety of physiological processes and in
disease states such as ischemia. Ischemic damage in the brain involves apoptotic cell death of
neurons as well as astrocytes and it has been suggested that reactive oxygen species (ROS)
generated as a consequence of ischemia are a major factor in triggering cell death. The waterpermeable
channel, aquaporin 4 (AQP4), which is expressed at high concentrations in astrocytes,
is an important determinant of mortality and morbidity in mice subjected to ischemia, however
the effects of ROS on AQP4 expression and the underlying mechanisms are still obscure. In the
present study, we used primary astrocyte cultures to examine the expression of AQP4 under
oxidative stress using hydrogen peroxide. First, we showed that H₂O₂ induces a significant
increase of both AQP4 mRNA and protein levels and that this effect is inhibited by the antioxidant
N-acetylcysteine. Second, we demonstrated using cell surface biotinylation that H₂O₂
increases AQP4 plasma membrane expression independently of the newly synthesized pool of
AQP4. In parallel, we found that caveolin-1 undergoes a dose- and time-dependent
phosphorylation in astrocytes treated with H₂O₂ and that this effect is inhibited by the src kinase
inhibitor PP2. More importantly, PP2 inhibits the H₂O₂-induced increase in AQP4 cell surface
expression, suggesting that the phosphorylation of caveolin-1 and possibly other proteins may
play a role in this process. To investigate this further, we used MDA-435 cells expressing Y14F
and Y14D caveolin-1 mutants transfected with AQP4 and found that these cells exhibit a
decrease and an increase in AQP4 membrane expression, respectively. Furthermore, caveolin-1
knock down in astrocytes inhibits H₂O₂-induced increase in AQP4 cell surface expression.
Together these findings show that the phosphorylation of caveolin-1 Y14 is a key regulator of
AQP4 cell surface expression in oxidative stress possibly by altering AQP4 internalization and
trafficking resulting in its redistribution within different compartments of the cell.
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Sklavounou, Evangelia. "Development and characterisation of an in vitro model of oxidative stress-induced cellular senescence and the evaluation of novel antioxidants." Thesis, University of Glasgow, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402011.
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Lima, Lorena PicanÃo de. "Effects of manual acupuncture and electroacupuncture on oxidative stress and inflammation in experimental model of cutaneous flaps randomised in rats." Universidade Federal do CearÃ, 2011. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13467.
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CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel SuperiorIschemia of the skin flaps increases the morbidity in surgical reconstruction procedures. Injuries resulting from the interruption or reduction of blood flow (ischemia) and are exacerbated by the reintroduction of oxygen-rich blood (reperfusion). Acupuncture (AC) promotes the stimulation of specific body points (acupoints) in order to achieve a therapeutic or homeostatic effect. Electroacupuncture (EA) is the application of electric current of low intensity and variable frequency through the needle inserted into specific acupoints previously. The choice of waveform, frequency and discharge intensity define the type of effect that will be reached. Whereas some published studies have demonstrated the protective effects of AC/EA in the preservation of skin flaps, this study aimed to investigate the effects of AC/EA in inflammation and oxidative stress in randomized skin flaps in rats. Forty rats were used in the study. Thirty-two animals underwent dorsal flap construction (8 x 2.5cm) and then were distributed randomly into 4 groups (n = 8): G-2 (surgical trauma), G-3 (Acupuncture), G -4 (2 Hz EA), G-5 (EA 100 Hz). The remaining 8 rats served as baseline control (G-1). All rats were anesthetized intraperitoneally with ketamine (90mg/kg) + xylazine (10mg/kg) on days 1, 3 and 7. In day 1 stainless steel needles were introduced in DM-14 [Dazhui], DM-2 [Yaoshu] and F-13 [Zhangmen] acupoints bilaterally in G3 rats.The acupoints are located, respectively, on the cranial, caudal edges and near the lateral edge of the skin flap. In G4, after insertion of needles, EA was applied (3Hz, 10 mA) for 30 minutes. The procedures were repeated on days 3 and 7. In G5 a frequency of 100Hz was used. Blood and skin samples were collected at the end of procedures (AC/AE) in groups G3, G4, G5, and after 30 minutes of anesthesia in G1/G2 rats for myeloperoxidase (MPO), malonaldehyde (MDA) and glutathione ( GSH) assays. The results were compared using the t test for unpaired samples. Skin MPO activity decreased significantly in G3 rats (6.41Â1.39 vs. 3.11Â2.80, p<0.001). There was also a significant decrease (6.41Â1.39 vs. 1.19Â0.39) of MPO activity with EA (3 Hz) and 100 Hz (6.41Âvs 1.39Â0.19) compared with G2. Plasma (6.56Â1.32 vs.21.48Â4.40) and tissue (54.15Â3.10 vs. 180.50Â10.35) GSH levels increased significantly in G3 rats. A significant increase in plasma and tissue GSH concentrations ocurred in G4/G5 rats. MDA levels increased significantly in groups G4/G5. Considering these results it is concluded that both AC/EA, applied to healthy rats, attenuate skin inflammatory response and reduce systemic and local oxidative stress, promoting an increase in plasma and tissue concentrations of GSH. On the other hand, EA has pro-peroxidative effect in plasma and skin of healthy rats subjected to surgical stress.
A isquemia dos retalhos cutÃneos aumenta a morbidade dos procedimentos em reconstruÃÃo cirÃrgica. As lesÃes decorrem da parada/reduÃÃo do fluxo sanguÃneo (isquemia) e sÃo agravadas pela reintroduÃÃo de sangue rico em oxigÃnio (reperfusÃo). Acupuntura (AC) promove a estimulaÃÃo de pontos especÃficos do corpo (acupontos) com objetivo de atingir um efeito terapÃutico ou homeostÃtico. Eletroacupuntura (EA) consiste na aplicaÃÃo de corrente elÃtrica de baixa intensidade e frequÃncia variÃvel atravÃs da agulha previamente inserida em determinado acupontos. A escolha do formato da onda, frequÃncia e intensidade da descarga definem o tipo de efeito que serà atingido. Considerando que alguns estudos publicados tÃm demonstrado os efeitos protetores da AC/EA na preservaÃÃo de retalhos cutÃneos, este estudo teve como objetivo investigar os efeitos da AC/EA no processo inflamatÃrio e no estresse oxidativo em retalhos cutÃneos randomizados, em ratos. Quarenta ratos foram utilizados no estudo. Trinta-e-dois animais foram submetidos à construÃÃo do retalho dorsal (8 x 2,5cm) e posteriormente distribuÃdos aleatoriamente em 4 grupos (n = 8): G-2 (trauma cirÃrgico); G-3 (Acupuntura); G-4 (EA 3Hz); G- 5 (EA 100Hz). Os 8 ratos restantes (G-1) serviram como controle basal. Todos os ratos foram anestesiados intraperitonealmente com cetamina (90mg/kg) + xilazina (10mg/kg) nos dias 1, 3 e 7. No dia 1, agulhas de aÃo inoxidÃvel foram introduzidas nos acupontos DM-14[Dazhui], DM-2[Yaoshu] e F-13[Zhangmen] bilateralmente, nos ratos do grupo G3. Esses acupontos se localizam, respectivamente, na borda cranial, caudal e prÃximo ao bordo lateral do retalho. No G4, apÃs a inserÃÃo das agulhas, foi aplicada uma estimulaÃÃo elÃtrica (3 Hz, 10 mA) durante 30 minutos. Os procedimentos foram repetidos nos dias 3 e 7. No G5 utilizou-se uma frequÃncia de 100Hz. Amostras de sangue e de pele foram coletadas ao termino dos procedimentos (AC/EA) nos grupos G3, G4, G5 e apÃs 30 minutos de anestesia nos grupos G1/G2, para dosagens de mieloperoxidase (MPO), Malonaldeido (MDA) e glutationa (GSH). Os resultados foram comparados utilizando-se o teste t para amostras nÃo pareadas. A AC diminuiu a atividade da MPO na pele dos ratos G3 (6,41 1,39 vs. 3,11 2,80, p<0,001). Houve tambÃm diminuiÃÃo significante (p<0,01) com a EA (3 Hz) (6,41Â1,39 vs. 1,19Â0,39, p<0,0001) e 100 Hz (6,41Â1,39 vs. 1,38Â0,19) comparados com o G2. A AC induziu aumento significante das concentraÃÃes de GSH no plasma (6,56Â1,32 vs. 21,48Â4,40) e na pele (54,15Â3,10 vs. 180,50Â10,35). Houve aumento significante as concentraÃÃes plasmÃticas e teciduais nos ratos do G4/G5. A concentraÃÃo de MDA aumentou significantemente nos grupos G4/G5. Considerando os resultados encontrados, conclui-se que a AC/EA atenuam a resposta inflamatÃria na pele e reduzem o estresse oxidativo sistÃmico e local, promovendo o aumento das concentraÃÃes plasmÃticas e teciduais de GSH. Por outro lado, a EA exerce efeito prÃ-peroxidativo no plasma e na pele de ratos sadios, submetidos ao estresse cirÃrgico.
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Posgai, Ryan T. "Development of a Drosophila melanogaster model system for nanoparticle toxicity assessment." University of Dayton / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1354252918.
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Marshall, Craig A., Ivan A. Borbon, and Robert P. Erickson. "Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease." SPRINGER HEIDELBERG, 2016. http://hdl.handle.net/10150/622828.
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Nicotinamide delivered in drinking water at about 2 g/kg/day significantly prolonged survival and showed a suggestive improvement on memory in the Npc1 (nih) / Npc1 (nih) mouse model of infantile NPC1 disease. It is likely that this role is due to its function as a histone deacetylase (HDAC) inhibitor although another HDAC inhibitor, valproic acid, was without effect. Nicotinamide could also work by preventing/reversing oxidative stress.
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Opii, Wycliffe Omondi. "OXIDATIVE STRESS AND REDOX PROTEOMICS STUDIES IN MODELS OF NEURODEGENERATIVE DISORDERS: I. THE CANINE MODEL OF HUMAN AGING; II. INSIGHTS INTO SUCCESSFUL AGING; AND III. TRAUMATIC BRAIN INJURY." UKnowledge, 2006. http://uknowledge.uky.edu/gradschool_diss/299.
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The studies presented in this dissertation were conducted with the objective ofgaining greater understanding into the mechanisms of successful aging, the role ofmitochondria dysfunction in traumatic brain injury, and also on the mechanisms ofimproved learning and cognitive function in the aging.Aging is usually characterized by impairments in physiological functionsincreasing its susceptibility to dementia and neurodegenerative disorders. In thisdissertation, the mechanisms of dementia-free aging were investigated. The use of anantioxidant fortified diet and a program of behavioral enrichment in the canine model ofhuman aging was shown to result in a significant decrease in the levels of oxidativestress. A proteomic analysis of these brains also demonstrated a significant decrease inthe oxidative modification of key brain proteins and an increase in the expression levelsof other key brain proteins associated with energy metabolism and antioxidant systemswhich correlated with improved learning and memory.We show that following TBI key mitochondrial-related proteins undergoextensive oxidative modification, possibly contributing to the severe loss ofmitochondrial energetics and neuronal cell death previously observed in experimentalTBI.Taken together, these findings support the role of oxidative stress in thepathophysiology of aging and age-related neurodegenerative disorders and in CNS injury.These studies also show that antioxidants and a program of behavioral enrichmentprovide protection against oxidative stress-mediated cognitive impairments.
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Kunsevi-Kilola, Carine. "The effect of Rooibos on trace elements absorption and biochemical parameters : a murine model." Thesis, Cape Peninsula University of Technology, 2014. http://hdl.handle.net/20.500.11838/2248.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2014.Over the past few decades, it has been shown that various critical diseases including heart disease, cancer, and diabetes associated with free radical generation and low endogenous antioxidant capacity, lead to oxidative stress and cell injury. In recent years, numerous studies have also reported that antioxidants, present in various beverages, vegetables and some foods have attracted a significant research interest due to their potential benefits to human health. However, epidemiological evidence shows a correlation between the intake of food rich in antioxidants and the reduced incidence of some mortality of chronic diseases, certain cancers and coronary heart disease. The aims of this study were to determine the effects of rooibos teas (fermented and unfermented) and green tea as a comparison on the biochemical parameters and the trace element absorption in a rat model. In this study 4 groups of experimental animals were used. All groups had ad libitum access to standard rat chow. Group A, the controls (11 animals), were fed with tap water; group B (11 animals) were fed with the liquid extract of fermented rooibos tea; group C (9 animals) were fed with the liquid extracts of unfermented rooibos and group 0 (9 animals) were fed with the liquid extract of green tea. All groups were fed for a period of 10 weeks. After the feeding period, the animals were sacrificed by euthanization with intraperitoneal injections of pentobarbital. Blood was sampled by cardiac puncture and centrifuged to obtain the serum. Some elemental analyses were performed with X-ray emission and backscattering. ICP-OES was used to determine the magnesium content. For X-ray emission, backscattering and ICP-OES analyses, 100 µL of each serum sample in a group were added to 2 ml freeze-drying tube. Of the combined specimen, 100 µL was used for the magnesium determination by ICP-OES. The remainder of the combined serum specimens for each group were freeze-dried at -80°C and then pressed into a pellet. The pellet was coated with carbon and analyzed using X-ray emission and backscattering. The elemental X-rays of P, S, Ca, Mn, Fe, Cu, Co, Zn, Mo, Ca and Se emitted were quantified to obtain the respective concentrations. Biochemical chemistry analyses were performed on each serum sample of each animal. The biochemical parameters tested for were total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, blood urea nitrogen, uric acid, total cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and creatinine.
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Murphy, Kyle Robert. "Nanosilver and CNT-Nanocomposite Toxicology in an In Vivo Model, D. Melanogaster." University of Dayton / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429977804.
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Cho, Hyung Joon. "Pro-oxidative and Pro-inflammatory Mechanisms of Brain Injury in Experimental Animal and 3D Cell Culture Model Systems." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/73476.
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The pro-oxidative and pro-inflammatory mechanisms have been implicated in various human diseases including neurological and psychiatric disorders. However, there is only limited information available on the etiology in the progression of neurological damage to brain. The emergence of tissue engineering with the growing interest in mechanistic studies of brain injury now raises great opportunities to study complex physiological and pathophysiological process in vitro. Therefore, the prime goals of this study include: (1) Determination of the molecular and cellular mechanisms responsible for blast- and radiation-induced brain injuries and (2) Development of a three-dimensional (3D) model system in order to mimic in vivo-like microenvironments to further broaden our knowledge in pro-oxidative and pro-inflammatory mechanisms and their cellular responses within 3D constructs.
In the first study, we demonstrated that blast exposure induced specific molecular and cellular alterations in pro-oxidative and pro-inflammatory environments in the brain and neuronal loss with adverse behavioral outcome. The results provide evidence that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in blast-induced neuronal loss and behavioral deficits.
In the second study, we investigated that fractionated whole-brain irradiation induced specific molecular and cellular alterations in pro-oxidative and pro-inflammatory environments in the brain along with elevation of reactive oxygen species (ROS)-generating protein (NOX-2) and microglial activation. Additionally, the contribution of NOX-2 in fractionated whole-brain radiation-induced oxidative stress was observed by dramatic amelioration of ROS generation after pharmacological inhibition of NOX-2. These results support that NOX-2 may play a pivotal role in fractionated whole-brain radiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain.
In the third study, we developed an in vitro 3D experimental model of brain inflammation by encapsulating microglia in collagen hydrogel with computational analysis of 3D constructs. The results indicated that our newly developed in vitro 3D model system provides a more physiologically relevant environment to mimic in vivo responses.
In conclusion, these data may be beneficial in defining a cellular and molecular basis of pathophysiological mechanisms of brain injuries. Furthermore, it may provide new opportunities for preventive and therapeutic interventions for patients with brain injuries and associated neurological disorders.Ph. D.
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NAGATA, KOHZO, TOYOAKI MUROHARA, SHOGO WATANABE, YUURI TAKESHITA, SAE OHURA, TAMAYO MURASE, TAKUYA HATTORI, MIWA TAKATSU, and KEIJI TAKAHASHI. "Premature Cardiac Senescence in DahlS.Z-Lepr fa/Lepr fa Rats as a New Animal Model of Metabolic Syndrome." Nagoya University School of Medicine, 2014. http://hdl.handle.net/2237/19482.
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Mizuta, Masanobu. "Effect of the Regulation of Oxidative Stress on Vocal Fold Wound Healing/ Expression of reactive oxygen species during wound healing of vocal folds in a rat model." Doctoral thesis, Kyoto University, 2015. http://hdl.handle.net/2433/199160.
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京都大学0048
新制・課程博士
博士(医学)
甲第18851号
医博第3962号
新制||医||1007(附属図書館)
31802
京都大学大学院医学研究科医学専攻
(主査)教授 別所 和久, 教授 鈴木 茂彦, 教授 瀬原 淳子
学位規則第4条第1項該当
Doctor of Medical Science
Kyoto University
DFAM
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Mizuta, Masanobu. "Effect of the Regulation of Oxidative Stress on Vocal Fold Wound Healing / Expression of reactive oxygen species during wound healing of vocal folds in a rat model." Kyoto University, 2003. http://hdl.handle.net/2433/199160.
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Maas, Dorothea Adriana. "Myelin Matters in Schizophrenia : Neurobiological Insights from Rat Model and Human Studies." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS530.pdf.
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La schizophrénie (SZ) est un trouble psychiatrique grave dont les symptômes cognitifs découlent d'un dysfonctionnement du cortex préfrontal (CPF) et impliquent une altération de la myélinisation et des anomalies interneuronales. Dans les chapitres 1 et 2 de cette thèse, j'ai introduit l'hypothèse que la myélinisation des interneurones de la parvalbumine est affectée en SZ et que des niveaux élevés de stress oxydatif interfèrent avec la différenciation des oligodendrocytes (OLs) et entravent ainsi la myélinisation correcte. En utilisant le modèle de rat APO-SUS, au chapitre 3, j'ai montré que le comportement cognitif dépendant du PFC est altéré, qu'il y a un défaut de différenciation OL et une hypomyélinisation de l'interneuron parvalbumine dans le PFC APO-SUS, et que l'enrichissement environnemental (EE) peut rétablir la différenciation OL, la myélinisation et le comportement cognitif des rats APO-SUS. Au chapitre 4, je montre qu'il y a un stress oxydatif dans l'APO-SUS mPFC, et que celui-ci est en partie à l'origine du défaut de différenciation APO-SUS OL. Notamment, le traitement antioxydant a sauvé le stress oxydatif, la myélinisation de l'interneuron ainsi que les troubles cognitifs chez les rats APO-SUS. Les membranes de la myéline sont principalement constituées de lipides, c'est pourquoi j'ai montré au chapitre 5 que l'expression des gènes liés aux lipides dans le SZ PFC était altérée, j'ai identifié une étiologie génétique commune entre le SZ et les lipides, et montré que la performance cognitive réduite des patients SZ était en corrélation avec une teneur réduite en lipides du PFCSchizophrenia (SZ) is a severe psychiatric disorder and its cognitive symptoms arise from prefrontal cortex (PFC) dysfunctioning and involve altered myelination and interneuron abnormalities. In Chapters 1 and 2 of this thesis, I have introduced the hypothesis that the myelination of parvalbumin interneurons is affected in SZ and that that high levels of oxidative stress interfere with the differentiation of oligodendrocytes (OLs) and as such hinder proper myelination. Using the APO-SUS rat model, in Chapter 3, I showed that PFC-dependent cognitive behaviour is impaired, there is an OL differentiation defect and parvalbumin interneuron hypomyelination in the APO-SUS PFC, and that environmental enrichment (EE) can restore OL differentiation, myelination and cognitive behaviour in APO-SUS rats. In Chapter 4, I show that there is oxidative stress in APO-SUS mPFC, and that this partially underlies the APO-SUS OL differentiation defect. Notably, antioxidant treatment rescued oxidative stress, interneuron myelination as well as cognitive defects in APO-SUS rats. Myelin membranes consist mainly of lipids, accordingly in Chapter 5 I show altered expression of lipid-related genes in SZ PFC, I identified shared genetic etiology between SZ and lipids, and showed that reduced cognitive performance of SZ patients was correlated with a decreased lipid content in the PFC
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Ozolins, Terence Robert Stanislavs. "Regulation of the transcription factor activator protein-1 (AP-1) in the whole rat embryo culture model in response to oxidative stress." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0015/NQ44545.pdf.
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Maglara, Antonia. "An investigation of the role of oxidative stress and the potential protective effect glutamine supplementation in an animal model of systematic inflammation." Thesis, University of Liverpool, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269718.
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Canda, Bartolomeu David. "Modulation of oxidative stress by rooibos (aspalathus linearis) herbal tea, chinese green (camellia sinensis) tea and commercial tea supplements using a rodent model." Thesis, Cape Peninsula University of Technology, 2012. http://hdl.handle.net/20.500.11838/1506.
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Thesis submitted in fulfillment of the requirements for the degree
Master of Technology: Biomedical Technology
In the Faculty of Health and Wellness Sciences
At the Cape Peninsula University of Technology, 2012Human and experimental animal studies have shown that biomarkers of oxidative damage are elevated in subjects with certain diseases or risk factors. Consequently, it is hypothesized that oxidative stress plays an important role in the pathogenesis of these diseases and that dietary intake of, or supplementation with antioxidants may be protective or be useful therapeutic targets. This study was designed to investigate the modulatory effect of Camellia sinensis (Chinese green tea), Aspalathus linearis (rooibos herbal tea) and the two commercial supplements on the antioxidant status of the liver and kidney of tert-butyl hydroperoxide (t-BHP)-induced oxidative stress male Wistar rats. Rooibos and green tea are beverages well-known for their antioxidant content. Based on the specific beverage consumed, sixty male Wistar rats were randomly assigned into six groups, i.e. fermented rooibos (FRT), unfermented rooibos (URT), Chinese green tea (CGT), rooibos supplement (RTS), Chinese green tea supplement (GTS) and control (CTL). The animals had free access to the respective beverages and standard diet for 10 weeks, while oxidative stress was induced during the last 2 weeks via intraperitoneal injection of 30 μM of t-BHP per 100 g body weight. Among all the beverage and/or supplement preparations, the commercial rooibos supplement had the highest total polyphenol content and antioxidant activity while fermented rooibos, as previously shown, had a lower antioxidant content and potency when compared to its unfermented counterpart. The ability of these beverages and/or supplements to modulate the antioxidant status in tissues was organ specific and varied according to the assessment method. When considering the liver, the intake of unfermented rooibos, Chinese green tea and the commercial rooibos supplement significantly (P<0.05) restored the t-BHP-induced reduction and increased the antioxidant status with regards to oxygen radical absorbance capacity and trolox equivalent antioxidant capacity (TEAC) levels. All the beverages and/or supplements also significantly (P<0.05) enhanced the renal antioxidant capacity as assessed by the TEAC assay. In what may be an indication of decreased oxidative stress, all the beverages were associated with a general decline in activities of the antioxidant enzymes which reached significant levels in renal superoxidase dismutase activity. Generally, the beverages did not impact significantly on lipid peroxidation (LPO) although there were differing trends in the two LPO markers assessed. While thiobarbituric acid reactive substances levels showed a declining trend in both tissues, the conjugated dienes were generally elevated. In conclusion, this study confirms Camellia sinensis and Aspalathus linearis as well as their two supplements as good sources of dietary antioxidants and results demonstrated that rooibos and green tea improved the liver and kidney antioxidant capacity of oxidative stress-induced rats. Their impact on antioxidant status in rats was shown to vary between organs and according to the method of assessment. Hence multi-method, multi-organ assessment may be a more informative approach in in vivo antioxidant studies.
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Paliobeis, Andrew S. "Effects of Pramlintide on Mitochondrial Dynamics and Health in the Alzheimer's Disease APP/PS1 Mouse Model." Kent State University Honors College / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1494262713896063.
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Steed, Kevin Sage. "Alzheimer's Disease and Diabetes: A Transgenic Mouse Model in Behavior, MRI, and Cells." BYU ScholarsArchive, 2018. https://scholarsarchive.byu.edu/etd/7460.
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Alzheimer's disease (AD) is the most common form of dementia, afflicting almost 5 million patients in the US, and impacting millions more, financially, physically and emotionally. Coming in as the 6th leading cause of death in the US, and showing no signs of slowing its annually increasing rates, the world is in desperate need of improved understanding of the disease's multifaceted pathogenesis and progression, more accurate forms of detection and diagnosis, and more effective prevention and treatment. While many are focused on the noble pursuit of understanding the genetic contributions to the appearance of the pathological amyloid beta (Aβ)) plaques and tau tangles seen in AD, the majority of cases are not explained by genes or allele risk. Instead environmental, dietary and lifestyle contributors may be the key to understanding, diagnosing and treating this awful disease. Diet especially may impact the body's ability to regulate oxidative stress, which will cause damage within the cell and lead to further dysregulation of iron storage and metabolism. Iron storage is heavily monitored through cellular mechanisms, and the way in which the body reacts involves creation of the Aβ plaques and tau tangles as receptacles for the molecule it has deemed as the cause of the problem, iron. We have aptly named our theory, the Iron Hypothesis, and in the following document will outline the evidence for this hypothesis, and the experiments designed and performed to prove it.First, we aimed to examine the impacts that various treatments would have on a transgenic in-vivo model, examining the cohorts' behavior over several time points. We report a significant difference in the behavioral measures of time, distance, errors and failed trials in the radial arm maze existed between genotype, treatment and sex of the mice. Tissue of the experimental mice was collected, but will be processed and analyzed at a later date.Secondly, we aimed to examine the same cohorts of the in-vivo mouse model for minute anatomical changes that took place over the course of the aforementioned behavioral trials using novel MRI scanning sequences sensitive to the low levels of iron build up. We report significant differences in the UTE scan measures for our western diet treatment at TE's of 1.2ms. Additionally, further investigation and optimization of the protocol may be required to further expand the findings.
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Sanjuán, Vázquez Myriam. "Study of proteins implicated in centronuclear myopathies by using the model of yeast Saccharomyces cerevisiae." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ021.
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La myopathie centronucléaire (CNM) est un groupe de maladies génétiques caractérisées au niveau histologique par des noyaux au centre des myofibres au lieu de la périphérie. Des mutations dans trois gènes (MTM1, DNM2 et BIN1) sont associées à cette pathologie. Récemment, l’implication d’un nouveau gène a été révélée dans une myopathie congénitale, le gène PYROXD1. Cependant, la base moléculaire responsable du déséquilibre à l'intérieur de la cellule reste incertaine et la relation entre le niveau histologique et les symptômes chez les patients n'est pas comprise. De plus, aucun traitement n'est disponible pour ces maladies. Au cours de ma thèse, j'ai centré mon travail sur l'utilisation du modèle de levure S. cerevisiae pour comprendre trois protéines associées au CNM : la myotubularine Mtm1, l'oxydoréductase Pyroxd1 et la dynamine Dnm2. Ces données révèlent qu’il est possible d’utiliser une simple cellule eucaryote afin d'élucider certains aspects moléculaires de ces protéines impliquées dans des maladies humainesCentronuclear myopathy (CNM) is a group of genetic disorders characterized at the histological level by nuclei at the center of the myofibers instead of the periphery. Mutations in three genes (MTM1, DNM2 and BIN1) are associated with this pathology. Recently the implication of a new gene has been revealed in a congenital myopathy, the PYROXD1 gene.However, the molecular basis responsible for the imbalance inside the cell remains unclear and the relation between the histological level and the symptoms in patients is not understood. Moreover, there is no treatment available for these diseases.During my thesis I have focused my work on using yeast S. cerevisiae model to understand three proteins associated to CNM: the myotubularin Mtm1, the oxidoreductase Pyroxd1 and the dynamin Dnm2. These data reveal that it is possible to use a single eukaryote cell to elucidate some molecular aspects of these proteins implicated in human disorders
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González, Alberth Jonnathan Carreño. "Avaliação da atividade neuroprotetora do ácido clorogênico no hipocampo de ratos wistar, submetidos a status epilepticus por lítio-pilocarpina." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-10052017-144511/.
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A epilepsia é uma enfermidade, caracterizada por eventos cerebrais paroxísticos auto-sustentados e recorrentes, que apresenta manifestações eletro-clínicas e neuropatológicas únicas, que podem alterar a estrutura e funcionamento do encéfalo, cujas manifestações são diferentes entre si. Afeta cerca de 50 milhões de pessoas no mundo. Modelos animais e ferramentas biológicas são importantes para se entender lesões neuroniais. Sabe-se que logo depois da administração de Li-Pilo em ratos - status epilepticus (SE), inicia-se uma cadeia de eventos neuroquímicos, como a produção de radicais livres,dentre outros, que podem piorar ou perpetuar as crises posteriores. A utilização de agentes antioxidantes, com ação no Sistema Nervoso Central pode significar uma alternativa co-adjuvante na prevenção das epilepsias secundárias, de animais de laboratório e talvez em humanos. Neste trabalho avaliou-se a ação antioxidativa e neuroprotetora do ácido clorogênico (AC), in vivo, em ratos submetidos ao SE. Comparou-se ademais o efeito do AC com o efeito de um antioxidante, o acido ascórbico. Ao tratar os animais com AC (30 mg/kg), houve uma diminuição significativa (50%), [F (7, 40)= 14,42; P < 0,0001], da produção de MDA, importante produto da peroxidação lipídica; assim como uma diminuição significativa (72%), [F (7,40)= 11,26; P < 0,0001], na atividade da SOD, enzima que atua como agente antioxidante endógeno. A ação do AC, diminuindo a concentração de MDA (49%), que é um dos substratos da SOD, levaria a uma menor taxa de SOD (59%). Pensando no que acontece com um fármaco que iniba essa cascata de peroxidação, esses resultados estão de acordo com a literatura, na qual se ressalta que a ação da SOD pode estar diretamente relacionada com a presença do MDA. E o mais importante, constatou-se que o AC (30 mg/kg) protegeu as células hipocampais, ou seja, diminuiu significativamente a perda de células nas regiões CA3 [F (4,25)= 15,55; P < 0,0001] (48%), e no hilus do hipocampo [F (4,25)= 6,276, P<0,0001] (75%). Da mesma forma, houve uma diminuição significativa de neurônios em degeneração (Fluoro Jade C+) na CA3 [F(2,15)= 40,90; P<0,0001]. Podemos concluir que o AC é um eficiente inibidor da proliferaçãode agentes oxidantes, que levam à morte celular, quando comparado com o ácido ascórbico, no hipocampo de ratos Wistar, quando induzido o SE com Li-Pilo. Portanto, sendo neuroprotetorEpilepsy is a disorder characterized by paroxysmal self-sustained and recurrent brain events, featuring electro-clinical and neuropathological phenomena unique, which may change the structure and functioning of the brain, whose manifestations are different. It affects about 50 million people worldwide. Animal models and are important biological tools for understanding neuronal injury. It is known that soon after the administration of Li-Pilo in rats - status epilepticus (SE), starts a chain of neurochemical events such as the production of free radicals, among others, that may worsen or perpetuate the subsequent seizures. The use of antioxidant agents acting on the central nervous system can alternatively mean a co-adjuvant in secondary preven-tion of epilepsy, laboratory animals and possibly humans. In our study we evaluated the antioxi-dative action and chlorogenic acid (CA) neuroprotective using Litio-Pilocarpine in vivo, in rats. It compared the effects of CA in addition to the effect of an antioxidant, ascorbic acid. By treating the animals with CA (30 mg / kg), a significant decrease in [F (7, 40) = 14.42; P <0.0001], the production of MDA, important product of lipid peroxidation; as well as a significant decrease in [F (7,40) = 11.26; P <0.0001] (50%), the activity of SOD, an enzyme that acts as an endogenous antioxidant. The action of CA, decreasing the concentration of MDA (49%), which is one of the SOD substrates, would lead to a lower rate of SOD (72%). Thinking about what happens to a drug that inhibits this peroxidation cascade, these results are consistent with the literature, in which it points out that the action of SOD can be directly related to the presence of MDA. Furthermore, it was found that the CA (30 mg / kg) protected the hippocampus cells, or significantly decreased cell loss in CA3 [F (4,25) = 15.55; P <0.0001] (59%), and hilus regions of the hippocampus [F (4,25) = 6.276, P <0.0001] (48%). Likewise, a significant reduction in neu-ronal degeneration (Fluoro Jade C +) in the CA3 [F (2,15) = 40.90; P <0.0001] (75%). We con-clude that the CA is an effective inhibitor of the proliferation of oxidizing agents, leading to cell death when compared to the ascorbic acid in the hippocampus of Wistar rats when induced SE with Li-Pilo. However, CA was neuroprotector in this model.
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Khan, J. "Investigation into the effects of specific muscarinic acetylcholine receptor antagonists on the myocardium in pre-clinical conditions of ischaemia reperfusion injury and oxidative stress model." Thesis, Coventry University, 2015. http://curve.coventry.ac.uk/open/items/3508a32c-8427-4ffe-9134-704a3e8c304b/1.
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Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors that mediate various actions of Acetylcholine (ACh) in the central nervous system and peripheral nervous system. In mammals, five distinct mAChR subtypes (M1-M5) have been recognised with the M2 subtype being predominantly present in the heart. The mAChR antagonists are routinely used for the treatment of various pathophysiological conditions including respiratory conditions. However, it has been postulated that mAChR antagonists may increase morbidity and mortality in chronic obstructive pulmonary disorder (COPD) and asthma patients with underlying cardiovascular disease, raising concerns regarding the cardiovascular safety of these agents. The current study was therefore undertaken to investigate the effects of individual mAChR antagonists in the setting of myocardial ischaemia reperfusion injury and oxidative stress models. We also investigated whether the inhibition of the mitochondrial permeability transition pore (MPTP) with cyclosporine-A (CsA) in the presence and absence of individual mAChR antagonists provided protection against ischaemia reperfusion injury. Furthermore, we also aimed to investigate the intracellular signalling pathway associated with mAChRs antagonists mediated myocardial injury under the stress conditions. Langendorff results showed that the non-selective M1-M3 mAChR antagonist, ipratropium bromide, the M2 mAChR antagonist, AF-DX 116 and the M3 mAChR antagonist, DAU 5884 significantly increased the infarct size to risk ratio of the heart in conditions of ischaemia and reperfusion. Detrimental effects of AF-DX 116 and DAU 5884 were abrogated by co-treatment of these drugs with mAChR agonist, acetylcholine (ACh) and/or CsA. Cell viability data of isolated cardiac myocytes revealed that AF-DX 116 and DAU 5884 caused a concentration dependent decrease in the viability of cardiac myocytes as well as causing a reduction in the time taken to depolarisation and hypercontracture under oxidative stress. AF-DX 116 and DAU 5884 significantly increased the levels of p-SAPK/JNK and decreased the levels of p-Akt and p-ERK. In addition, ACh and CsA showed to activate p-Akt and p-ERK. To conclude, the data suggest that AF-DX 116 and DAU 5884 caused cardiotoxicity at cellular, tissue and protein level in conditions of ischaemia reperfusion injury and oxidative stress. Furthermore, inhibition of the mitochondrial transition pore with CsA protected against the AF-DX 116 and DAU 5884 induced injury via activation of the pro-survival proteins, p-Akt and p-ERK.
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Ratti, James A. "INVESTIGATING SMOKE EXPOSURE AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WITH A CALIBRATED AGENT BASED MODEL (ABM) OF IN VITRO FIBROBLAST WOUND HEALING." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5441.
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COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate parameter-sets for each cell type using in vitro data of scratch-induced migration, viability, senescence-associated beta-galactosidase and alpha-smooth muscle actin expression. Parameter sensitivities around each calibrated parameter-set were analyzed. This model represents the prototype of a tool designed to explore fibroblast functions in the pathogenesis of COPD and evaluate potential therapies.
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Helou, Doumet. "Rôle du facteur de transcription Nrf2 dans la régulation des fonctions du neutrophile in vitro et dans l’allergie cutanée." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS305/document.
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Les neutrophiles constituent une première ligne de défense contre les agents infectieux. En revanche, leur activation incontrôlée peut exacerber certaines pathologies inflammatoires telles que les allergies cutanées. Notre équipe a montré précédemment que le facteur de transcription Nrf2 connu pour son rôle anti-oxydant, régulait l’inflammation cutanée dans l’hypersensibilité de contact (HSC). Ainsi ce travail a été mené pour évaluer in vitro l’implication de la voie Nrf2 dans les fonctions des neutrophiles et pour identifier son rôle dans le recrutement et l’activation des neutrophiles dans l’HSC.In vitro, nous montrons que la protéine Nrf2 est fortement exprimée dans les neutrophiles de la moelle osseuse. Nrf2 est fonctionnelle dans les neutrophiles stimulés : il active la transcription de gènes cibles cytoprotecteurs et diminue celle des gènes de l’inflammation. Ainsi, le prétraitement des neutrophiles avec un activateur de Nrf2 tel que le sulforaphane, réduit la production des formes réactives de l’oxygène (FRO)en réponse à une stimulation. En parallèle, l’absence de Nrf2 ne semble pas affecter la phagocytose et la nétose, deux fonctions clés du neutrophile. Enfin, Nrf2 est indispensable pour une migration optimale des neutrophiles en réponse aux chimiokines.Au cours de l’HSC induite par le dinitrochlorobenzène (DNCB), Nrf2 régule indirectement le recrutement des neutrophiles, en contrôlant le stress oxydant cutané et les voies inflammatoires impliquées dans la production de chimiokines, notamment CCL2, CCL4 et CCL11. En outre, Nrf2 induit l’augmentation d’expression du scavenger CD36 dans les macrophages et augmente ainsi leur capacité à éliminer les neutrophiles apoptotiques pour initier la résolution de l’inflammation.En conclusion, l’activation de Nrf2 dans les neutrophiles participe au contrôle de la production des FRO et la migration. En outre, Nrf2 émerge comme un effecteur clé dans le contrôle du recrutement et de la clairance des neutrophiles au cours de la réponse inflammatoire cutanée aux molécules allergisantes. La mise en évidence de ces mécanismes protecteurs de Nrf2 nous permet de proposer cette protéine comme nouvelle cible thérapeutique dans le contrôle d’inflammations cutanées chroniquesNeutrophils form the first line of defense against infectious agents. However, their uncontrolled activation may exacerbate certain inflammatory conditions such as cutaneous allergies. Our team has previously shown that Nrf2 transcription factor known for its antioxidant role, regulates skin inflammation in contact hypersensitivity (CHS). Thus, our work was carried out to evaluate in vitro the involvement of Nrf2 pathway in neutrophil functions and to identify Nrf2 role in neutrophil recruitment and activation in CHS.In vitro, we showed that the protein Nrf2 was highly expressed in bone marrow neutrophils. Nrf2 is functional in stimulated neutrophils: it activates the transcription of cytoprotective genes and downregulates that of inflammatory genes. Thus, pretreatment of neutrophils with an Nrf2 activator such as sulforaphane reduces the production of reactive oxygen species (ROS) in response to stimulation. In parallel, Nrf2 does not affect two key functions of neutrophil, phagocytosis and netosis.Finally, Nrf2 is essential for optimal migration of neutrophils toward chemokines. In CHS induced by the dinitrochlorobenzene (DNCB), Nrf2 indirectly regulates the recruitment of neutrophils, through regulation of skin oxidant stress and inflammatory pathways that are involved in chemokines production, including CCL2, CCL4 and CCL11. In addition, Nrf2 induces the up-regulation of scavenger CD36 in macrophages and thus increases their ability to eliminate apoptotic neutrophils leading to the resolution of inflammation.In conclusion, Nrf2 activation in neutrophils participates in the control of ROS production and migration. In addition, Nrf2 emerges as an important effector in the control of neutrophil recruitment and clearance during the skin inflammatory response to allergenic molecules. The demonstration of Nrf2 protective mechanisms leads us to suggest this protein as a new therapeutic target in the control of chronic skin inflammations
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Adhikari, Rajan Deep. "MRI T2 Signal Changes Indicate Tau Pathophysiology in a Murine Alzheimer's Disease Model." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6944.
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Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for AD, inducing oxidative stress to elevate intracellular iron, and analyze its co-localization with proteins using Magnetic Resonance Imaging (MRI), 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Western blot. We report three primary findings: 1) a significant loss in T2 signal over bilateral hippocampi of transgenic mice compared to the wild types (WT) by three months, corresponding to early disease and the ability of proteins to sequestration iron. Ability of rescue treatments to impede disease progression reflected as preserved T2 signal intensities over these areas throughout our study period of nine months. 2) Concentration of zinc and its dual role in the presence or absence of oxidative stress reflected as loss of 1H NMR T2 measurement showed that higher concentrations of zinc were neuro protective when there was an active oxidative stress inducing condition, but neurotoxic and promote oxidative damage in normal condition. And 3) Different strains of mice, according to their transgene, expressed various proteins associated with AD. However, these expressions were in accordance with our iron-hypothesis.
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Queiroz, Ana Isabelle de Gois. "Efeitos do dimesilato de lisdexanfetamina em ratos: relevÃncia como modelo animal do episÃdio de mania." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10261.
Full textAbstract:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorO Transtorno Afetivo Bipolar à um transtorno mental severo que acomete cerca de 1,5% da populaÃÃo mundial e se caracteriza pela oscilaÃÃo de humor entre a depressÃo e a mania, interferindo no desempenho do indivÃduo em termos pessoais e profissionais, bem como sendo responsÃvel por alto nÃmero de suicÃdios. Todos esses fatores o caracterizam como um problema de saÃde pÃblica. Seu mecanismo fisiopatolÃgico ainda nÃo à totalmente conhecido e o arsenal terapÃutico atual ainda à escasso, necessitando de contÃnuas pesquisas nesse Ãmbito. Observando a necessidade de maior disponibilidade de modelos animais de mania para maiores pesquisas à que o estudo objetivou investigar um novo modelo animal de mania. O desenho experimental da pesquisa seguiu os critÃrios para determinar um modelo animal que sÃo: a validade de face (onde busca-se mimetizar no animal comportamento caracterÃstico na doenÃa), validade de constructo (a fisiopatologia da doenÃa) e a validade preditiva ( se os medicamentos jà estabelecidos para determinada doenÃa sÃo capazes de reverter e prevenir os efeitos do fÃrmaco que induz a patologia). Logo, o presente trabalho se propÃs a investigar a atividade do Dimesilado de Lisdexanfetamina (LDX), prÃ-fÃrmaco que ao ser metabolizado a d-anfetamina passa a exercer sua atividade psicoestimulante como possÃvel agente em um modelo animal de mania. O tratamento com D-ANF induz hiperlocomoÃÃo e à considerado como um modelo animal de mania bipolar jà estabelecido. Por isso, procurou-se determinar as alteraÃÃes comportamentais e de estresse oxidativo induzidas pela administraÃÃo via oral sub-crÃnica de LDX, bem como a reversÃo e prevenÃÃo deste efeito ao tratar os ratos com lÃtio, medicamento protÃtipo como estabilizante do humor. Um aumento significativo no comportamento locomotor foi induzido por LDX (10 e 30 mg/Kg). Para determinar os efeitos de LÃtio (Li) nas alteraÃÃes induzidas por LDX nos ratos do grupo reversÃo, o protocolo seguiu a administraÃÃo de LDX (10 ou 30 mg / Kg) ou soluÃÃo salina durante 14 dias. Entre os dias 8o e 14o os animais receberam Li (47,5 mg / kg, ip) ou soluÃÃo salina. No protocolo de prevenÃÃo, os ratos foram prÃ-tratados com soluÃÃo salina ou Li antes da administraÃÃo de LDX. Os nÃveis de Glutationa Reduzida (GSH) e de peroxidaÃÃo lipÃdica foram determinados no cÃrtex prÃ-frontal (PFC), hipocampo (HC) e estriado (ST) de ratos. Constatou-se que o LÃtio preveniu a hiperlocomoÃÃo induzida por LDX, nas doses de 10 e 30 mg/kg, mas somente reverteu a hiperlocomoÃÃo quando utilizada a dose de 10 mg/ kg de LDX. AlÃm disso, ambas as doses de LDX diminuÃram o conteÃdo de GSH (em ST e PFC), enquanto que Li foi capaz de reverter e prevenir estas alteraÃÃes, principalmente no PFC. LDX (10 e 30 mg / kg) aumentou a peroxidaÃÃo lipÃdica, que foi revertida e prevenida por Li. Diante dos resultados em termos de hiperlocomoÃÃo e estresse oxidativo demonstrou-se que o LDX conseguiu induzir tais parÃmetros, se mostrando como uma promessa de modelo animal alternativo de mania.
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Wu, Wing Man. "An investigation into the neuroprotective effects of estrogen and progesterone in a model of homocysteine-induced neurodegeration." Thesis, Rhodes University, 2006. http://hdl.handle.net/10962/d1003284.
Full textAbstract:
Homocysteine (Hcy) is a sulfur containing amino acid and is a potent neurotoxin. It has been shown that elevated levels of Hcy, termed hyperhomocysteinemia, plays a role in the pathologies of Alzheimer’s disease (AD) and age-related cognitive decline. Hcy is a glutamate agonist, which causes in increase in Ca[superscript (2+)] influx via the activation of NMDA class of excitatory amino acid receptors, which results in neuronal cell death and apoptosis. Estrogen and progesterone are female hormones that are responsible for reproduction and maternal behaviour. However, in the last decade, it is evident that both female hormones have neuroprotective properties in many animal models of neurodegeneration. Collectively, both estrogen and progesterone reduce the consequences of the oxidative stress by enhancing the antioxidant defence mechanisms, reducing excitotoxicity by altering glutamate receptor activity and reducing the damage caused by lipid peroxidation. However, the mechanisms by which estrogen and progesterone provide such neuroprotection probably depend on the type and concentration of hormone present. Moreover, numerous studies have shown that hormone replacement therapy (HRT, estrogen and progestins) or estrogen-only replacement therapy (ERT) may prevent or delay the onset of AD and improve cognition for women with AD. Clinical trials have also shown that women taking HRT may modify the effects of Hcy levels on cognitive functioning. Oxidative stress increases in the aging brain and thus has a powerful effect on enhanced susceptibility to neurodegenerative disease. The detection and measurement of lipid peroxidation and superoxide anion radicals in the brain tissue supports the involvement of free radical reactions in neurotoxicity and in neurodegenerative disorders. The hippocampus is an important region of the brain responsible for the formation of memory. However, agents that induce stress in this area have harmful effects and could lead to dementia. This study aims to investigate and clarify the neuroprotective effects of estrogen and progesterone, using Hcy-induced neurodegenerative models. The initial studies demonstrate that estrogen and progesterone have the ability to scavenge potent free radicals. Histological studies undertaken reveal that both estrogen and progesterone protect against Hcy-induced neuronal cell death. In addition, immunohistochemical investigations show that Hcy-induced apoptosis in the hippocampus can be inhibited by both estrogen and progesterone. However, estrogen also acts at the NMDA receptor as an agonist, while progesterone blocks at the NMDA receptor. These mechanisms reduce the ability of Hcy to cause damage to neurons, since Hcy-induced neurotoxicity is dependent on the overstimulation of the NMDA receptor. SOD and GPx are important enzymatic antioxidants which can react with ROS and neutralize them before these inflict damage in the brain. Hcy can increase oxidative stress by inhibiting expression and function of these antioxidants. However, it has been shown that the antioxidant abilities of both estrogen and progesterone can up-regulate the activities of SOD and GPx. These results provide further evidence that estrogen and progesterone act as antioxidants and are free radical scavengers. The discovery of neuroprotective agents is becoming important as accumulating evidence indicates the protective role of both estrogen and progesterone in Hcy-induced neurodegeneration. Thus further work in clinical trials is needed to examine whether reducing Hcy levels with HRT can become the treatment of neurodegenerative disorders, such as Alzheimer’s disease.
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Bader, Lange Miranda Lu. "IN VIVO OXIDATIVE STRESS IN ALZHEIMER DISEASE BRAIN AND A MOUSE MODEL THEREOF: EFFECTS OF LIPID ASYMMETRY AND THE SINGLE METHIONINE RESIDUE OF AMYLOID-β PEPTIDE." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/117.
Full textAbstract:
Studies presented in this dissertation were conducted to gain more insight into the role of phospholipid asymmetry and amyloid-β (Aβ)-induced oxidative stress in brain of subjects with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). AD is a largely sporadic, age-associated neurodegenerative disorder clinically characterized by the vast, progressive loss of memory and cognition commonly in populations over the age of ~65 years, with the exception of those with familial AD, which develop AD symptoms as early as ~30 years-old. Neuropathologically, both AD and FAD can be characterized by synapse and neuronal cell loss in conjunction with accumulation of neurofibrillary tangles and senile plaques. Elevated levels of oxidative stress and damage to brain proteins, lipids, and nucleic acids are observed, as well. Likewise, aMCI, arguably the earliest form of AD, displays many of these same clinical and pathological characteristics, with a few exceptions (e.g., no dementia) and to a lesser extent.
Studies in this dissertation focused on the contributions of oxidative stress to the exposure of phosphatidylserine (PtdSer) to the outer-leaflet of the lipid membrane, how and when PtdSer asymmetric collapse contributes to the progression of aMCI, AD, and FAD, and the role played by methionine-35 (Met-35) of Aβ in oxidative stress and damage, as measured in a transgenic mouse model of Aβ pathology. Normally, the PtdSer is sequestered to the cytosolic, inner-leaflet of the bilayer by the adenosine triphosphate (ATP)-dependent, membrane-bound translocase, flippase, which unidirectionally transports PtdSer inward against its concentration gradient. Oxidative stress-induced modification of flippase and/or PtdSer, however, leads to prolonged extracellular exposure of PtdSer on the outer membrane leaflet, a known signal for both early apoptosis and selective recognition and mononuclear phagocytosis of dying cells. Within the inferior parietal lobule (IPL) of subjects with aMCI and AD, a significant collapse in PtdSer asymmetry was found in association with increased levels of both pro- and anti-apoptotic proteins, Bax, caspase-3, and Bcl-2. Moreover, a significant collapse in PtdSer asymmetry was also found in whole brain of human double-mutant knock-in mouse models of Aβ pathology, together with significantly reduced Mg2+ATPase activity, representing flippase activity, and increased levels of pro-apoptotic caspase-3. Significant PtdSer externalization corresponded to the age at which significant soluble Aβ(1-42) deposition occurs in this particular mouse model (9 months), and not of plaque deposition (12 months), suggesting that elevated levels of Aβ(1-42), together with increasing oxidative stress and apoptosis, may contribute to altered PtdSer membrane localization.
Also in this dissertation, transgenic mice carrying Swedish and Indiana mutations on the human amyloid precursor protein (APPSw,In) and APPSw,In mice carrying a Met35Leu mutation on Aβ were derived to investigate the role of Met-35 in Aβ(1-42)-induced oxidative stress in vivo. Oxidative stress analyses revealed that Aβ-induced oxidative stress requires the presence of Met-35, as all indices of oxidative damage (i.e., protein carbonylation, nitration, and protein-bound 4-hydroxy-2-trans-nonenal [HNE]) in brain of Met35Leu mice were completely prevented. Moreover, immunohistochemical analyses indicated that the Met35Leu mutation influences plaque formation, as a clear reduction in Aβ-immunoreactive plaques in Met35Leu mice was found in conjunction with a significant increase in microglial activation. In contrast, behavioral analyses suggested that spatial learning and memory was independent of Met-35 of Aβ, as Met35Leu mice demonstrated inferior water-maze performance compared to non-transgenic mice.
Differential expression and redox proteomic analyses to pinpoint proteins significantly altered by the APPSw,In and Met35Leu mutations was performed, as well. Expression proteomics showed significant increases and decreases in APPSw,In and Met35Leu mouse brain, respectively, in proteins involved in cell signaling, detoxification, structure, metabolism, molecular chaperoning, protein degradation, mitochondrial function, etc. Redox proteomics found many of these same proteins to be oxidatively modified (i.e., protein carbonylation and nitration) in both APPSw,In and Met35Leu mouse brain, providing additional insights into the critical nature of Met-35 of Aβ for in vivo oxidative stress in a mammalian species brain, and strongly suggesting similar importance of Met-35 of Aβ(1-42) in brain of subjects with aMCI and AD. Taken together, studies presented in this dissertation demonstrate the role of oxidative stress-induced alteration of PtdSer asymmetry and Met-35 in Aβ-induced oxidative stress in aMCI, AD, and FAD brain.
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Sanders, Lisa Merle. "Effects of dietary fat and fiber on the oxidative status of the small intestine and colon of rats." Diss., Texas A&M University, 2005. http://hdl.handle.net/1969.1/3764.
Full textAbstract:
Colon cancer is one of the most commonly diagnosed cancers in the US, yet small intestine cancer is a rare event. While there are many similarities between these two tissues, inherent differences such as redox status, may contribute to the variation in cancer occurrence. We examined the difference in reactive oxygen species (ROS) generation, antioxidant enzyme activity and oxidative DNA damage in the small and large intestine of rats under normal conditions and following exposure to exogenous oxidative stress. Basal ROS and antioxidant enzyme activities were greater in the colon than the small intestine, and the balance of ROS to antioxidant enzymes in the colon was more pro-oxidant than in the small intestine. During oxidative stress, ROS and oxidative DNA damage were greater in the colon than the small intestine. Thus the colon responds to oxidative stress less effectively than the small intestine, possibly contributing to increased cancer incidence at this site. We next wanted to understand how diets containing a combination of fish or corn oil and pectin or cellulose may alter the redox environment of the colon. ROS, oxidative DNA damage, antioxidant enzyme activity and apoptosis were measured in colonocytes of rats fed one of four diets containing either corn oil or fish oil and cellulose or pectin. Measurements were madein rats untreated with carcinogen and rats exposed to a chemical carcinogen and radiation. In rats not treated with a carcinogen, fish oil enhanced ROS, and fish oil/pectin suppressed antioxidant enzymes as compared to corn oil/cellulose. Oxidative DNA damage was inversely related to ROS in the fish oil/pectin diet and apoptosis was enhanced relative to other diets. In carcinogen treated and irradiated rats, a similar protective effect was seen with fish oil/pectin as evidenced by a reduction in oxidative DNA damage and enhancement of apoptosis. This suggests that a diet containing fish oil/pectin may protect against colon carcinogenesis by modulation of the redox environment to promote apoptosis and minimize oxidative DNA damage.