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Cochemé, Helena Margaret. "Yeast as a model for investigating mitochondrial oxidative damage." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614040.
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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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Hall, James. "The oxidative stability of FAME in the model Crankcase environment." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/39341.
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The use of biodiesel has increased in recent years due to the implementation of governmental policies driven by environmental, economic and political reasons. Biodiesel is composed of fatty acid methyl esters (FAME), which can be derived from plant, marine and animal sources. There have been reports of some potential problems associated with biodiesel use in modern diesel engines, with lubricant dilution by blended biodiesel fuels leading to accumulation of FAME in the oil sump in the crankcase. This project focuses on the design and implementation of an experimental model based on the Rancimat apparatus that can simulate certain aspects of the FAME degradation chemistry occurring in the crankcase and oil sump. An analysis procedure to compliment the experimental model is applied to carry out product distribution analysis on a series of (C18) model FAME, identifying and quantifying the oxidation products formed under the experimental conditions, where epoxides are the major monomeric degradation. Some oxidation kinetic parameters have been investigated using biodiesel samples, with noticeable differences in oxidation rates found when FAME are oxidised individually and when in mixtures. Kinetic factors of FAME and model base oil in single and multi-component systems have also been investigated, with the base oil displaying good oxidative stability in mixtures as well as on its own The influence of antioxidants on stabilising various model systems has shown synergistic effects. Combinations of primary and secondary antioxidants have displayed good synergy, with the suppression of the rate of hydroperoxide formation by primary antioxidants enhancing the effectiveness of the secondary antioxidant. Primary antioxidants have been observed to affect the onset of oxidation, whilst secondary antioxidants decrease the hydroperoxide and epoxide, but increase the alcohol yields as a result of autoxidation.
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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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Mortimer, D. N. "Metalloporphyrin-catalysed model systems for the cytochrome P450-dependent mono-oxygenases." Thesis, University of York, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374188.
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Zhang, Xiankuan. "Studies of methane oxidative coupling with practical catalysts and model systems." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386819.
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Tonami, Hiroyuki. "Oxidative Polymerization of Phenolic Compounds Catalyzed by Peroxidase and Its Model Complex." 京都大学 (Kyoto University), 2003. http://hdl.handle.net/2433/77757.
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Jennings, John Adam. "HETEROGENEOUS BASE METAL CATALYZED OXIDATIVE DEPOLYMERIZATION OF LIGNIN AND LIGNIN MODEL COMPOUNDS." UKnowledge, 2017. http://uknowledge.uky.edu/chemistry_etds/81.
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With the dwindling availability of petroleum, focus has shifted to renewable energy sources such as lignocellulosic biomass. Lignocellulosic biomass is composed of three main constituents, lignin, cellulose and hemicellulose. Due to the low value of cellulosic ethanol, utilization of the lignin component is necessary for the realization of an economically sustainable biorefinery model. Once depolymerized, lignin has the potential to replace petroleum-derived molecules used as bulk and specialty aromatic chemicals. Numerous lignin depolymerization strategies focus on cleavage of β-aryl ether linkages, usually at high temperatures and under reductive conditions.
Alternatively, selective benzylic oxidation strategies have recently been explored for lignin and lignin models. In this work, heterogeneous catalytic methods using supported base metals and layered-double hydroxides were evaluated for the oxidation of lignin models both before and after benzylic oxidation. Additionally, by studying putative reaction intermediates, insights were gained into the mechanisms of oxidative fragmentation of the model compounds.
Generally, it was found that after benzylic oxidation models were more susceptible to oxidative fragmentation. Indeed, several heterogeneous oxidation systems were found to convert lignin models to oxygenated aryl monomers (mainly benzoic acids and phenols) using inexpensive primary oxidants (i.e., hydrogen peroxide and molecular oxygen). Reactions were conducted at relatively mild temperatures and at low oxygen concentrations for the purpose of an easy transition to large-scale experiments. Finally, the catalytic systems that resulted in significant cleavage of lignin models were applied to a Kraft lignin. Oxidation of Kraft lignin resulted a mixture of products for which analytical data and increased solubility are consistent with interunit cleavage within the lignin macromolecule.
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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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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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Williamson, Beth. "Determinants of transcriptional regulation of transport and oxidative processes in human model systems." Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/15053/.
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Initial predictions of drug response and drug-drug interactions (DDIs) are made following high-throughput in vitro screening. Such assays are indispensible in the pharmaceutical industry to determine the metabolism, transport and pharmacokinetics of new chemical entities. However, they often fail when extrapolated to in vivo response due to unsuitable pharmacokinetic or pharmacodynamic prediction. The primary aim of this thesis was to investigate and understand the differences in the expression profiles of drug disposition genes, between transformed hepatic cell lines and primary human hepatocytes. Primary human hepatocytes were also analysed to determine uptake contribution, induction and genotype of key drug disposition-relevant genes. The loss of hepatic phenotype in HepG2 and Huh7 cells is partly due to the altered expression of transcriptional regulators including; chaperones, co-chaperones, co-activators and co-repressors. Indeed, Chapter 2 of this thesis shows lower levels of the Gadd45β and PGC1α gene expression in HepG2 cells corresponds to a deficient expression and activity of cytochrome P450 3A4 (CYP3A4), with the levels reducing further as cell passage increases, in comparison to primary human hepatocytes. HepG2 cells were transfected with a novel complex transfection of Gadd45β and PGC1α with the aim to improve CYP3A4 activity in Chapter 3. CYP3A4 activity was improved by 54% and induction response was enhanced in comparison to control cells with no off-target effects. Over the last decade it has become apparent that transporters can play a significant role in the disposition of many drugs. Organic anion transporting polypeptide (OATP) transporters have received considerable recent attention since they mediate sodium-independent uptake of a broad array of xenobiotics. A method to determine the specific contribution of OATP1B1 in the hepatic uptake was successfully optimised and applied for 5 therapeutic drugs in Chapter 4. Future application of this strategy is likely to have broad importance in determining relative contribution that individual transporters play in drug disposition. To prevent accumulation and toxicity of xenobiotics, biotransformation and transport of foreign compounds occurs. However, these processes can be altered by induction or inhibition mechanisms. Rifampicin is a first line drug in tuberculosis (TB) treatment but it is a potent inducer of CYPs and transporters. DDIs during TB treatment are common but the induction potential of different rifamycins has not been comprehensively ranked. Chapter 5 investigated the induction potential of rifampicin, rifapentine and rifabutin. Rifampicin significantly induced CYP3A4, ABCB1, OATP1B1 and ABCC2 in primary human hepatocytes. Induction by rifabutin was observed for CYP3A4, OATP1B3 whilst rifapentine only significantly induced OATP1B1. This work serves as a basis for further study into the extent to which rifamycins induce key metabolism and transporter genes. Nuclear receptors (NR) regulate the expression of CYPs and drug transporters influencing pharmacokinetics. PXR and VDR have been found to synergistically increase CYP3A4 expression and activity in intestinal cell lines. This effect has been observed in vivo with seasonal variations apparent for CYP3A4 substrates. In Chapter 6, novel associations between vitamin D receptor polymorphisms and expression of it and its target genes involved in drug disposition were shown in D2 intestinal biopsies. This thesis reports generation of model systems and their application to enable many questions to be answered relating to pharmacokinetics and DDIs. The thesis forms a solid platform from which to further investigate these issues in future studies.
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Beurle, Darcy [Verfasser]. "A micro-mechanically motivated model for the oxidative ageing of elastomers / Darcy Beurle." Hannover : Gottfried Wilhelm Leibniz Universität Hannover, 2020. http://d-nb.info/1215423489/34.
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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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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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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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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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Miller, Larry M. "A model for the prediction of thermo-oxidative mass loss of ceramic coated polyimide composites." Ohio : Ohio University, 1995. http://www.ohiolink.edu/etd/view.cgi?ohiou1174609538.
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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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Bankoglu, Ezgi Eylül [Verfasser], and Helga [Gutachter] Stopper. "Oxidative status and genomic damage in an obesity model / Ezgi Eylül Bankoglu. Gutachter: Helga Stopper." Würzburg : Universität Würzburg, 2016. http://d-nb.info/1112466339/34.
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Yao, Soledad G. "OXIDATION OF β-O-4 LIGNIN MODEL COMPOUNDS AND APPLICATION TO LIGNIN LINKAGE DEGRADATION FACILITATED BY MECHANOCHEMICAL TREATMENT AND TWO-STEP OXIDATIVE DEPOLYMERIZATION." UKnowledge, 2018. https://uknowledge.uky.edu/chemistry_etds/91.
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The oxidation of lignin model compounds was studied in conventional solvents in parallel with oxidations in ionic liquid solvents. Catalyst systems were investigated in ionic liquid solvents to determine how reaction rates and the selectivity for benzylic carbon oxidation were affected. Oxidation rates were often lower in ionic liquids than in conventional solvents ‒ as indicated by lower conversion in a standard reaction time ‒ likely due, at least in part, to the higher viscosity of ionic liquids. Mechano chemical treatment of Indulin AT kraft lignin by ball milling with KOH and toluene produced significant carbonyl functionality, among other changes. The chemical reactivity of the lignin was increased, resulting in greater lignin degradation from porphyrin oxidation followed by Baeyer-Villiger oxidation. The mechanochemical treatment produced a level of lignin oxidation that was similar to that produced by porphyrin-catalyzed oxidation. Combining mechanochemical treatment with porphyrin oxidation produced a synergistic positive effect on the depolymerization of lignin, as demonstrated by a significantly higher yield of monomers. The methyl ester of vanillic acid was obtained as the main monomeric product (after methylation), along with a small amount of methyl 5-carbomethoxyvanillate.
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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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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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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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Mottweiler, Jakob [Verfasser]. "Transition metal-catalyzed oxidative cleavage of lignin and lignin β-O-4 model compounds / Jakob Mottweiler." München : Verlag Dr. Hut, 2016. http://d-nb.info/1100968946/34.
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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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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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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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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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Fukuoka, Tokuma. "Synthesis of novel functional polymeric materials via oxidative coupling of phenols by peroxidase and its model complex." 京都大学 (Kyoto University), 2005. http://hdl.handle.net/2433/144883.
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Lopes, Fernanda Martins. "Parkinson's disease : experimental in vitro model validation and the potential role of cofilin-1 in the pathophysiological mechanisms." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/159503.
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The dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) is responsible for the marked motor impairment observed in Parkinson's disease (PD). However, the molecular mechanisms underlying this are not completely understood. Since by the time of diagnosis, 50-70% of the dopaminergic neurons of the nigrostriatal pathway have already been degenerated, it is difficult to investigate the early-stage events of disease pathogenesis. Due to inaccessibility of the human brain to study initial pathogenic mechanisms of the disease, experimental models have been developed in an attempt to elucidate PD etiology and its progression. Nevertheless, PD models are a controversial issue in neuroscience research since it is challenging to mimic human neuronal complexity. Therefore, the lack of optimal models that recreate disease pathology is one of the causes of failure of clinical trials that have attempted to find new/better PD therapies. Taking this in consideration, the development of more suitable models is necessary to improve our knowledge regarding PD etiological mechanisms. Additionally, the understanding of the advantages and disadvantages of models already established would also be beneficial for PD research, which our group addressed by reviewing this subject. Considering this, we chose SH-SY5Y cells as a PD model for our studies. To investigate the initial stages of PD-induced neurodegeneration, our work focused in the role of cofilin-1, a protein involved in mitochondrial dysfunction caused by oxidant-induced-apoptosis, which are two pathogenic processes strongly related to PD. Hence, in the thesis, we aimed to validate the use of retinoic-acid-(RA)-differentiated SH-SY5Y cells as an in vitro model and use it to investigate the potential role of cofilin-1 in the initial molecular and cellular mechanisms of PD. Although SH-SY5Y cells are widely used in PD research, their major drawback is their lack of important neuronal features, such as low levels of proliferation and stellate morphology. On the other hand, SH-SY5Y cells can acquire a neuronal phenotype when treated with differentiation agents such as RA. Since several protocols have been described, the consequence of which may be the discrepancies observed among studies regarding neuronal and dopaminergic features. In Chapter I, we aimed to validate a RA-differentiation protocol for SH-SY5Y cells previously established by our research group, focusing upon characterization of neuronal features and its subsequent response to 6-hydroxydopamine (6-OHDA), a toxin widely used to induce dopaminergic degeneration. RA-differentiated SH-SY5Y cells have low proliferative rates, a pronounced neuronal morphology and high expression of genes related to synapse vesicle cycle, dopamine synthesis/degradation, and dopamine transporter (DAT). After exploring phenotypic differences between these two models, we verified that RA-differentiated cells were more sensitive to 6-OHDA toxicity than undifferentiated cells, which could be related to an increase of DAT immunocontent. Many lines of evidence have showed that DAT is responsible for 6-OHDA uptake in vivo. Once inside the neuron, 6-OHDA underwent auto-oxidation causing a significant increase in oxidative stress. However, toxin uptake is not an essential step in undifferentiated SH-SY5Y cells, as auto-oxidation occurs extracellularly. We showed here, for the first time, that RA-differentiated SH-SY5Y cells can mimic, at least in part, an important mechanism of the 6-OHDA-induced cell death found in previous in vivo studies. Hence, the cellular model established by our research group presents essential neuronal features, being a suitable model for PD research. In Chapter II, RA-differentiated SH-SY5Y cells were used as cellular model to investigate disease molecular mechanisms, focusing upon cofilin-1. Our previous data have shown that oxidation of non-phosphorylate (activated) cofilin-1 leads to mitochondrial dysfunction and cell death induced by apoptosis in tumour cells. Here we found that cofilin-1 played a role in early stages of neuronal apoptosis induced by 6-OHDA in our cellular model since cofilin-1 mitochondrial translocation precedes organelle dysfunction. Overexpression of wild type CFL1 resulted in increased sensitivity of SH-SY5Y cells to 6-OHDA-induced neuronal cell death. Furthermore, overexpression of non-oxidizable CFL1 containing Cys-to-Ala mutations (positions 39, 80 and 139) increased neuronal resistance to this toxin, suggesting that oxidation is an important step in 6-OHDA toxicity. Follow-up experiments were performed in order to evaluate clinically whether cofilin-1 pathway proteins content is altered in PD post mortem human brain. Our findings showed a significant decrease in p-cofilin-1/cofilin-1 ratio in PD patients, which indicates an increase in the amount of activated cofilin-1 available for oxidation. Moreover, through principal component analysis, the immunodetection of cofilin-1 pathway proteins were able to discriminate controls and PD individuals during the early-stage of neuropathological changings. Hence, we demonstrated, for the first time, a possible role for cofilin-1 in PD pathogenesis and its potential use as biomarker. Taken together, our data showed that RA-differentiated SH-SY5Y cells present terminally-differentiated dopaminergic neuron features, that are essential to mimic dopaminergic neurons. By using this cellular model and post mortem brain tissue, we also demonstrated a possible role for cofilin-1 in early steps of the neurodegeneration process found in PD, which it could impact drug and biomarker discovery researches.
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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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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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Möller, Marisa. "Oxidative status in rats exposed to social isolation rearing : behavioral pharmacology studies and relevance for schizophrenia / Marisa Moller." Thesis, North-West University, 2009. http://hdl.handle.net/10394/5091.
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PURPOSE: Psychotic (positive) symptoms are the most distinctive feature of schizophrenia, although negative symptoms such as emotional flattening, social withdrawal and cognitive disturbances are the most treatment resistant manifestation of the illness. Schizophrenia is a progressive degenerative illness that has been causally linked to environmental and neurodevelopmental factors, as well as dysfunctional redox balance. Validated animal models are useful in identifying and studying novel neurobiological targets for neuropsychiatric illnesses. Post weaning social isolation rearing (SIR) in rats has been proposed to model the neurodevelopmental aspects of schizophrenia. We validated the SIR model with respect to effects on sensorimotor gating and social interaction, deficits of which are core symptoms of schizophrenia. Following this, effects on the levels of oxidative stress were determined in the frontal cortex and striatum of rats exposed to SIR, two brain regions strongly implicated in the pathology of schizophrenia. Finally, in order to more closely relate these bio-behavioural changes to the human condition, we studied the overall effect of sub-chronic treatment with the atypical antipsychotic, clozapine, on the above described behavioural and neurochemical parameters.
METHODS: Male Sprague-Dawley (SD) rats (10 rats/group) were used. In a non-treatment arm, four groups of rats were randomly separated at weaning and exposed to either 8 weeks SIR or 8 weeks social rearing. At the respective time point of 8 weeks two groups were subjected to behavioural testing of mean startle amplitude (at 120dB) and percentage prepulse inhibition (%PPI) of the acoustic startle (AS) reflex (at 72, 76, 80 and 86dB prepulse), and various social interactive and self-directed behaviours were accessed using the open field test (OFT). The remaining two groups were sacrificed at 8 weeks and brain tissue was harvested for analysis of superoxide dismutase activity, oxidized (GSSG) versus reduced (GSH) glutathione ratio, and levels of lipid peroxidation, in the frontal cortex and striatum. In the treatment arm, consisting out of eight groups of animals, four groups of SIR rats received either saline or clozapine (5mg/kg i.p.) for the last 11 days of SIR. The remaining four groups were socially reared and also received either saline or clozapine treatment as above. At 8 weeks, four groups were subjected to behavioural testing as described above and a parallel neurochemical study was performed using the same layout as above, except that after the 8 weeks, neurochemical redox analysis were done as described above. Mixed statistical modelling with repeated measures and appropriate post hoc tests were used to access the effects of SIR with and without treatment on PPI and mean startle. Social interaction in SIR and socially reared animals, with and without treatment, was analyzed using 1-way ANOVA with suitable post hoc testing. Mixed linear models with repeated measures and appropriate post hoc tests were used for analysis of the redox data in SIR and socially reared animals, with and without treatment.
RESULTS: In the non-treatment arm, %PPI was significantly reduced in SIR versus socially reared rats. Deficits in various social interactive behaviours were observed in SIR versus group-housed rats, as well as increased locomotor activity and self-grooming. Superoxide dismutase activity and oxidized versus reduced glutathione ratio were significantly decreased, together with a significant increase in products of lipid peroxidation, in isolation reared versus socially reared rats.
Following clozapine treatment, %PPI in isolates was significantly elevated by clozapine versus saline treatment (i.e. reversed the effect of SIR). %PPI was unaltered in socially reared animals receiving either treatment. As with the non-treatment group, social interactive behaviours were significantly impaired in isolates receiving saline, while locomotor activity and self-grooming were increased. SIR rats receiving only saline showed similar altered redox state as the non-treatment groups, while clozapine treatment effectively reversed deficits in %PPI, aberrant social behaviours and redox alterations in the SIR rats, with limited to no effects in the socially reared controls.
CONCLUSION: SIR thus significantly disrupts sensorimotor gating and social behaviours in male Sprague-Dawley rats, while at the same time evokes a significant disruption of redox state in both the frontal cortex and striatum of these animals, with distinct evidence for increased oxidative stress in these brain regions. Importantly, both altered behaviour and redox state are reversed by sub-chronic clozapine treatment. SIR is therefore a useful, non-lesion and non-pharmacological neurodevelopmental animal model of schizophrenia that presents with robust face, predictive and possibly construct validity for schizophrenia.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2010.
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Liu, Longcheng. "Oxidative Dissolution of Spent Fuel and Release of Nuclides from a Copper/Iron Canister : Model Developments and Applications." Doctoral thesis, KTH, Kemiteknik, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3292.
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Three models have been developed and applied in the performance assessment of a final repository. They are based on accepted theories and experimental results for known and possible mechanisms that may dominate in the oxidative dissolution of spent fuel and the release of nuclides from a canister. Assuming that the canister is breached at an early stage after disposal, the three models describe three sub-systems in the near field of the repository, in which the governing processes and mechanisms are quite different. In the model for the oxidative dissolution of the fuel matrix, a set of kinetic descriptions is provided that describes the oxidative dissolution of the fuel matrix and the release of the embedded nuclides. In particular, the effect of autocatalytic reduction of hexavalent uranium by dissolved H2, using UO2 (s) on the fuel pellets as a catalyst, is taken into account. The simulation results suggest that most of the radiolytic oxidants will be consumed by the oxidation of the fuel matrix, and that much less will be depleted by dissolved ferrous iron. Most of the radiolytically produced hexavalent uranium will be reduced by the autocatalytic reaction with H2 on the fuel surface. It will reprecipitate as UO2 (s) on the fuel surface, and thus very little net oxidation of the fuel will take place. In the reactive transport model, the interactions of multiple processes within a defective canister are described, in which numerous redox reactions take place as multiple species diffuse. The effect of corrosion of the cast iron insert of the canister and the reduction of dissolved hexavalent uranium by ferrous iron sorbed onto iron corrosion products and by dissolved H2 are particularly included. Scoping calculations suggest that corrosion of the iron insert will occur primarily under anaerobic conditions. The escaping oxidants from the fuel rods will migrate toward the iron insert. Much of these oxidants will, however, be consumed by ferrous iron that comes from the corrosion of iron. The nonscavenged hexavalent uranium will be reduced by ferrous iron sorbed onto the iron corrosion products and by dissolved hydrogen. In the transport resistance network model, the transport of reactive actinides in the near field is simulated. The model describes the transport resistance in terms of coupled resistors by a coarse compartmentalisation of the repository, based on the concept that various ligands first come into the canister and then diffuse out to the surroundings in the form of nuclide complexes. The simulation results suggest that carbonate accelerates the oxidative dissolution of the fuel matrix by stabilizing uranyl ions, and that phosphate and silicate tend to limit the dissolution by the formation of insoluble secondary phases. The three models provide powerful tools to evaluate "what if" situations and alternative scenarios involving various interpretations of the repository system. They can be used to predict the rate of release of actinides from the fuel, to test alternative hypotheses and to study the response of the system to various parameters and conditions imposed upon it.QC 20100521
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Nilsson, Sara. "Radiation induced dissolution of model compounds for spent nuclear fuel : mechanistic understanding of oxidative dissolution and its inhibition." Doctoral thesis, KTH, Kärnkemi (stängd 20110630), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-95433.
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This doctoral thesis is focused on radiation induced oxidative dissolution of UO2, Pd-doped UO2, SIMFUEL (as model substances for spent nuclear fuel) and UN (a possible future fuel) and inhibition of the oxidative dissolution. H2O2 is assumed to be the most important oxidant for spent nuclear fuel dissolution under deep repository conditions. The dissolution of uranium has been studied by oxidation by added H2O2 and by gamma irradiation in the presence and absence of carbonate. In carbonate free solutions very low amounts of uranium are dissolved from UO2 due to formation of metastudtite, UO4·2H2O on the UO2 surface which blocks the surface from further oxidation. Metastudite formation was confirmed with Raman spectroscopy. In the presence of carbonate, the concentration of dissolved uranium increases linearly over time for UO2 and UN, due to the complex formation between carbonate and oxidized uranium. For SIMFUEL a large fraction of H2O2 is consumed by catalytic decomposition under all conditions examined. This results in very low amounts of uranium released. Metastudtite formation was not observed on SIMFUEL. The oxidation during gamma radiolysis shows a larger difference in dissolution rates between UO2 and UN in carbonate solutions compared to upon oxidation by added H2O2. UN was found to have a lower dissolution rate, most probably because 50 % more oxidant is needed to reach the soluble U(VI). It was shown that the redox reactivity of UO2 appears to increase ~1.3 times, after being irradiated at doses > 40 kGy. The effect is permanent and delayed. The presence of sulfide shows an inhibiting effect on radiation induced dissolution due to scavenging of radiolytic oxidants and reduction of U(VI). The catalytic properties of Pd (as a model for the noble metal particles containing Mo, Ru, Tc, Pd and Rh, formed by the fission products) are examined. It was found that Pd has a catalytic effect on the reaction between H2O2 and H2 and the second order rate constant is determined to (2.1±0.1)x10-5 m s-1. The reaction between UO2 and H2O2 is catalyzed by Pd. Pd also has a catalytic effect on the reduction of U(VI) by H2 both in aqueous solution, rate constant (1.5±0.1)x10-5, and in the solid phase, rate constants 4x10-7 m s-1 and 7x10-6 m s-1 for pellets with 1 and 3 % Pd respectively. These values are very close to the diffusion limit for these systems. The catalytic effect was not influenced by the presence of sulfide. The catalytic effect in the solid phase reduction shows that the expected conditions in a deep repository, 40 bar H2 and 1 % noble metal particle content, is sufficient to stop the dissolution.QC 20120530
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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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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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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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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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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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Steele, Allison M. "NEW INSIGHTS INTO POST-SEPSIS MUSCLE WEAKNESS ELUCIDATED USING A NOVEL ANIMAL MODEL." UKnowledge, 2017. https://uknowledge.uky.edu/physiology_etds/37.
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Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild to induce muscle weakness or too severe and cause death within a few days. As such, this dissertation work first focused on establishing a clinically-relevant animal model of sepsis which yields surviving mice with chronic skeletal muscle weakness (Aim 1). This aim involved refining the cecal slurry injection model of polymicrobial sepsis in young adult animals, as well as optimizing the timing, duration, and dose of multiple therapeutic agents. The resulting resuscitation protocol was adapted for use in late-middle-aged animals, and muscle strength was evaluated using an ex vivo system which confirmed significant muscle weakness in sepsis survivors, long after sepsis was resolved. Next, using this novel model, we sought to characterize sepsis-induced long-term muscle dysfunction at the molecular level (Aim 2). The first set of experiments under this aim was designed to identify the primary global mechanism(s) (i.e. atrophy, polyneuropathy, and/or myopathy) responsible for muscle weakness in sepsis survivors. Analysis of the force-frequency curves and specific force measurements led to the conclusion that myopathy is the primary cause. Electron micrograph observation, functional assays, and protein analysis then showed that sepsis survivors’ skeletal muscles are characterized by profound mitochondrial abnormalities and oxidative damage. Collectively, these studies demonstrate that long-term muscle weakness is apparent in sepsis-surviving animals, and the functional decline is associated with unresolved mitochondrial damage and dysfunction. This work suggests that medical treatments beyond targeting muscle wasting alone could allow sepsis survivors to regain function and return to productive lives.
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Araujo, Luiz Felipe Lopez. "Efeitos da administração sistêmica de metilprednisolona em pulmões de ratos doadores em morte encefálica submetidos a transplante pulmonar." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/71631.
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INTRODUÇÃO: O transplante pulmonar é a única opção terapêutica para determinados pacientes com doença pulmonar em estágio terminal. A maioria dos transplantes de pulmão é realizada a partir de doadores em morte encefálica, condição que per si pode comprometer o sucesso do procedimento. A fisiopatologia da morte encefálica é complexa e envolve mecanismos hemodinâmicos, simpáticos e inflamatórios. A administração de metilprednisolona 60 minutos após indução da morte encefálica reduz a atividade inflamatória em pulmões de ratos. OBJETIVO: Avaliar os efeitos do tratamento com metilprednisolona em pulmões de ratos transplantados a partir de ratos doadores induzidos à morte encefálica quando administrada 60 minutos após indução da mesma. MÉTODOS: doze ratos Wistar foram randomizados e anestesiados em 2 grupos (n=6): controle: indução de morte encefálica e administração de solução salina; metilprednisolona (MET): indução de morte encefálica e administração de metilprednisolona 60 minutos após. Os animais foram observados e ventilados por 120 minutos e depois submetidos a transplante pulmonar. Foram avaliados parâmetros hemodinâmicos e gasométricos, escore histológico, dosagem de substâncias reativas ao ácido tiobarbitúrico (TBARS), superóxido dismutase (SOD), TNF-α e interleucina-1β (IL-1β). RESULTADOS: houve redução significativa dos níveis de TNF-α e IL-1β no grupo que recebeu metilprednisolona (p=0,0084; p=0,0155, respectivamente). Não houve diferença significativa na atividade do TBARS e SOD entre os grupos controle e MET (p=0,2644; p=0,7461, respectivamente). Não houve diferença significativa na gasometria, nos parâmetros hemodinâmicos, e nas alterações histológicas entre os grupos controle e MET. CONCLUSÃO: a utilização de metilprednisolona após a morte encefálica em ratos doadores reduz a atividade inflamatória em pulmões transplantados, mas não tem influencia sobre o estresse oxidativo.INTRODUCTION: Lung transplantation is the only therapeutic option for a subset of patients with end-stage lung disease. Most lung transplantations are performed using brain-dead donors, a condition that compromises the success of the procedure. The physiopathology of brain death is complex and involves haemodynamics, the sympathetic nervous system and inflammatory mechanisms. Administering methylprednisolone 60 minutes after inducing brain death in rats has been shown to modulate pulmonary inflammatory activity. OBJECTIVE: To evaluate the effects of methylprednisolone on transplanted rat lungs from donors treated 60 minutes after brain death. METHODS: Twelve Wistar rats were anaesthetised and randomly assigned to 1 of 2 groups (n=6): a control group that underwent the induction of brain death and the administration of saline solution and a methylprednisolone (MET) group that underwent the induction of brain death and the administration of methylprednisolone after 60 minutes. All of the animals were observed and ventilated for 120 minutes and then submitted to lung transplantation. We evaluated haemodynamic and blood gas parameters, the histologic score, the lung tissue determination of thiobarbituric acid-reactive substances (TBARS), the level of superoxide dismutase (SOD), the level of TNF-α and the level of interleukin-1β (IL-1β). RESULTS: There was a significant reduction in the levels of TNF-α and IL-1β in the group that received methylprednisolone (p=0.0084 and p=0.0155, respectively). There were no significant differences in TBARS and SOD between the control and MET groups (p=0.2644 and p=0.7461, respectively). There were no significant differences in the blood gas parameters, the haemodynamic parameters and the histologic alterations between the control and MET groups. CONCLUSION: The administration of methylprednisolone after brain death in donor rats reduces inflammatory activity in transplanted lungs but has no influence on oxidative stress.
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Andrade, José Antenor Araújo de. "Efeito da deficiência de tiamina sobre a inflamação, estresse oxidante e migração celular em modelo experimental de sepse." Universidade do Estado do Rio de Janeiro, 2012. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=5769.
Full textAbstract:
A sepse é uma condição de elevada letalidade muito frequente em pacientes graves e pode estar associada à deficiência de vitamina B1 ou tiamina. Sendo a tiamina fundamental para produção de energia, restauração do poder redutor e síntese de ribose e desoxirribose celulares, o objetivo deste estudo foi avaliar o efeito da deficiência de tiamina sobre a resposta inflamatória, através da medida de interleucinas, o estresse oxidante, pela determinação do 4-hidróxi 2-nonenal (4-HNE) um produto de peroxidação de lipídeos de membrana e a migração celular em modelo experimental de sepse. Em um primeiro experimento foi determinada a concentração de pirofosfato de tiamina (PPT) no sangue de camundongos c57bl6 alimentados com ração completa e com ração deficiente em tiamina, para determinação do tempo necessário para a indução de deficiência dessa vitamina. Em um segundo experimento foi utilizada a ligadura e perfuração cecal (CLP) como modelo de sepse em quatro grupos: SHAM ração completa, SHAM ração deficiente em tiamina, CLP ração completa, CLP ração deficiente em tiamina. As concentrações de PPT no sangue foram determinadas por cromatografia líquida de alta eficiência. As dosagens séricas e no líquido peritoneal de TNF-α, IL-1β, IL-6, KC e MCP-1/CCL2 foram realizadas por ELISA. O nível de 4-hidroxi,2-nonenal (4-HNE) no fígado foi avaliado por Western Blot. Contagem de leucócitos no sangue e no líquido peritoneal foi feita por microscopia óptica. Foi avaliada a concentração de bactérias no líquido peritoneal. Nos animais alimentados com ração completa a concentração média de PPT foi 303 42,6 nM, e a deficiência de tiamina foi induzida após 10 dias de ingestão da ração pobre em tiamina, quando observou-se concentração de 12,5 2,4 nM. No lavado peritoneal dos animais submetidos à CLP e privados de tiamina observou-se nível significativamente maior de TNF-α e MCP-1. A IL-1β foi menor no sangue do mesmo grupo. A expressão de 4-HNE foi maior nos grupos privados de tiamina. Quanto à celularidade sanguínea, observou-se apenas maior contagem de mononucleares no grupo submetido à CLP e privado de tiamina. No líquido peritoneal, a contagem de leucócitos totais, mononuleares e monócitos foi mais elevada nos grupos CLP, mas sem relação com o tipo de dieta. No entanto, no líquido peritoneal o grupo CLP deficiente em tiamina revelou população bacteriana significativamente menor que o grupo alimentado com ração completa e os grupos sham. Concluiu-se que a deficiência de tiamina associou-se com aumento da morte bacteriana na cavidade peritoneal, aumento do estresse oxidante, e mudanças na resposta inflamatória.
Palavras-chave: Tiamina. Sepse. Estresse oxidante. Inflamação. Modelo de sepse.A sepse é uma condição de elevada letalidade muito frequente em pacientes graves e pode estar associada à deficiência de vitamina B1 ou tiamina. Sendo a tiamina fundamental para produção de energia, restauração do poder redutor e síntese de ribose e desoxirribose celulares, o objetivo deste estudo foi avaliar o efeito da deficiência de tiamina sobre a resposta inflamatória, através da medida de interleucinas, o estresse oxidante, pela determinação do 4-hidróxi 2-nonenal (4-HNE) um produto de peroxidação de lipídeos de membrana e a migração celular em modelo experimental de sepse. Em um primeiro experimento foi determinada a concentração de pirofosfato de tiamina (PPT) no sangue de camundongos c57bl6 alimentados com ração completa e com ração deficiente em tiamina, para determinação do tempo necessário para a indução de deficiência dessa vitamina. Em um segundo experimento foi utilizada a ligadura e perfuração cecal (CLP) como modelo de sepse em quatro grupos: SHAM ração completa, SHAM ração deficiente em tiamina, CLP ração completa, CLP ração deficiente em tiamina. As concentrações de PPT no sangue foram determinadas por cromatografia líquida de alta eficiência. As dosagens séricas e no líquido peritoneal de TNF-α, IL-1β, IL-6, KC e MCP-1/CCL2 foram realizadas por ELISA. O nível de 4-hidroxi,2-nonenal (4-HNE) no fígado foi avaliado por Western Blot. Contagem de leucócitos no sangue e no líquido peritoneal foi feita por microscopia óptica. Foi avaliada a concentração de bactérias no líquido peritoneal. Nos animais alimentados com ração completa a concentração média de PPT foi 303 42,6 nM, e a deficiência de tiamina foi induzida após 10 dias de ingestão da ração pobre em tiamina, quando observou-se concentração de 12,5 2,4 nM. No lavado peritoneal dos animais submetidos à CLP e privados de tiamina observou-se nível significativamente maior de TNF-α e MCP-1. A IL-1β foi menor no sangue do mesmo grupo. A expressão de 4-HNE foi maior nos grupos privados de tiamina. Quanto à celularidade sanguínea, observou-se apenas maior contagem de mononucleares no grupo submetido à CLP e privado de tiamina. No líquido peritoneal, a contagem de leucócitos totais, mononuleares e monócitos foi mais elevada nos grupos CLP, mas sem relação com o tipo de dieta. No entanto, no líquido peritoneal o grupo CLP deficiente em tiamina revelou população bacteriana significativamente menor que o grupo alimentado com ração completa e os grupos sham. Concluiu-se que a deficiência de tiamina associou-se com aumento da morte bacteriana na cavidade peritoneal, aumento do estresse oxidante, e mudanças na resposta inflamatória.Sepsis is a prevalent condition in critically ill patients and may be associated with thiamine deficiency (TD). Since thiamine is important for energy production, redactor power recovering and ribosis and desoxirribosis synthesis, the aim of this study was to evaluate TD effect in inflammation, oxidative stress and cell recruitment in a sepsis model. Thiamine pyrophosphate (TPP) normal concentration was determined in blood of c57bl6 mice fed with AIN93G chow and also in animals fed with similar AIN93G chow without thiamine in order to determine the time required to produce TD. Another experiment was carried out with cecal ligation and puncture (CLP) as the sepsis model with four groups: SHAM with AIN93G complete chow, SHAM with TD chow, CLP with AIN93G complete chow and CLP with TD chow. TPP blood concentrations were determined by HPLC/Fluorescence. Blood and peritoneal liquid TNF-alpha, IL-1, IL-6, KC and MCP-1/CCL2 determinations were performed by ELISA. The expression of 4-HNE was performed by Western Blot. Blood and peritoneal liquid leukocytes counting were performed by optical microscopy. Peritoneal liquid bacterial concentration was determined. Blood TPP mean concentration in AIN93G complete chow was 287.9 27.8 nM and TD occurred in 10 days in TD chow group and blood concentration in this group was 12.5 2.4 nM. Peritoneal liquid TNF-alpha and MCP-1 concentrations were significantly greater in CLP with TD chow group than the other groups. Blood IL1-β was lower in the same group. Liver 4-HNE expression was highest in TD groups. Blood mononuclear number was greater in CLP TD chow group the others. Peritoneal liquid leukocites, mononuclears and neutrophils numbers were detected in greater number in the same group. However, peritoneal liquid bacterial concentration was significantly lower in the same group. In coclusion TD was associated with greater bacterial killing in peritoneal liquid, greater oxidative stress and change in inflammatory response.
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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.
Full textAbstract:
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.