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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
111

Physiologically-obtainable polyphenol exposures modulate reactive oxygen and nitrogen species signaling in the C2C12 model of skeletal muscle ageing

Hayes, N., Fogarty, M., Sadofsky, L., Jones, Huw 28 August 2024 (has links)
Yes / Age-related frailty is a significant health and social care burden, with limited treatment options. There is a lack of suitable cell culture model for screening large numbers of test compounds to identify those which promote healthy skeletal muscle function. This paper describes the characterization of reactive oxygen and nitrogen species (RONS) signalling changes in young and aged myoblasts and myotubes using C2C12 cells, and the application of aged cultures to assess the effect of dietary polyphenols on RONS signalling. Aged myoblasts and myotubes showed significantly increased reactive oxygen species (p < 0.01 and p < 0.001 respectively), nitric oxide (p < 0.05 for myoblasts and myotubes), and lipid peroxidation (p < 0.05 for myoblasts and myotubes). Nine polyphenols were assessed in aged myoblasts and myotubes using concentrations and incubation times consistent with known pharmacokinetic parameters for these compounds. Although several polyphenols were seen to reduce single markers of RONS signalling, only kaempferol and resveratrol significantly reduced multiple markers in both cell models. Modulation of enzymatic antioxidant activities was assessed as a possible mechanism of action, although superoxide dismutase and catalase activities were significantly reduced in aged (versus young) myotubes (p < 0.01 and p < 0.05 respectively), no effect of polyphenol treatment on these enzyme activities were observed. Overall, this research has shown the utility of the C2C12 model (myoblasts and myotubes) for screening compounds in aged muscle, and that resveratrol and kaempferol (using pharmacokinetically-informed exposures) can modulate RONS signalling in skeletal muscle cells after an acute exposure. / NH is supported by a University of Hull-funded PhD studentship.
112

The effects of acute interval exercise and strawberry intake on postprandial lipemia

O'Doherty, A.F., Jones, Huw, Sathyapalan, T., Ingle, L., Carroll, S. 29 April 2020 (has links)
Yes / Purpose: Raised postprandial triglycerides (TAG) and related oxidative stresses are strongly associated with increased cardiovascular disease (CVD) risk. Acute exercise and strawberry ingestion independently ameliorate postprandial lipid excursions and oxidative stress. However, the combined effects of these lifestyle interventions is unknown. We investigated whether acute exercise and strawberry consumption improved postprandial responses to an oral fat tolerance test (OFTT) in overweight/obese males. Methods: Overweight/obese adult males underwent four separate OFTT (73g fat, 33g carbohydrate) with blood sampled at baseline and hourly for 4 h after OFTT. Two OFTT contained 25g freeze-dried strawberries and two contained strawberry flavouring (placebo). Participants performed 40 minutes of submaximal high intensity interval cycling exercise (HIIE) 16 h before one strawberry and one placebo OFTT, and rested before the remaining two OFTT. Serum TAG was analysed and TAG area under curve (AUC) and incremental AUC (iAUC) were calculated. Oxidative stress markers were measured at baseline and 4 h. Differences between conditions (strawberry/placebo and exercise/rest) were assessed using repeated measures ANOVA. Results: Ten males (Age, 31.5 IQR 17.8 years; BMI, 29.9 ±1.8 kg.m-2) completed the study. TAG AUC was 1.5 mmol.4h-1.L-1 lower for the exercise conditions compared to the rest conditions (95% confidence interval [CI]= -2.3 to 0.8, p= 0.001). TAG AUC was not different between the strawberry and placebo conditions (CI= -1.3 to 0.6, p= 0.475). TAG iAUC was 0.5 mmol.4h-1.L-1 greater for the strawberry compared to the placebo conditions (CI= 0.1 to 1.0, p= 0.021). There were no changes in markers of lipid related oxidative stress (P> 0.05). Conclusion: Acute submaximal HIIE appears effective in reducing postprandial lipaemia in overweight/obese adult males. However, strawberry ingestion did not improve postprandial TAG.
113

Resistant maltodextrin as a shell material for encapsulation of naringin: Production and physicochemical characterization

Pai, D.A., Vangala, Venu R., Ng, J.W., Tan, R.B.H. January 2015 (has links)
Yes / Herein the potential of a relatively new water soluble fiber, resistant maltodextrin (RMD) to encapsulate grapefruit polyphenol, naringin, using spray drying was evaluated. Full factorial Design Of Experiments (DOE) for spray drying with two levels of fiber–naringin ratio and spray dryer inlet temperature was executed. Resulting powders were characterized with respect to particle size and morphology, crystallinity, thermal properties, moisture sorption and naringin aqueous solubility increase. A 60–80% encapsulation was achieved. Thermal and moisture sorption behaviors of these dispersions were found to be dominated by RMD. By varying fiber–naringin ratio and spray drying temperatures, naringin was able to disperse in amorphous form in RMD matrix, which led to 20–55% increase in aqueous solubility. Solubility enhancement was found to correlate positively with increasing fiber: naringin ratio and spray drying temperature due to multiple factors discussed in this study. In conclusion, fiber–polyphenol bicomponent nutraceutical was successfully developed based on a well-established encapsulation technology i.e. spray-drying.
114

Managing Apple Maturity and Storage to Increase the Quality of Virginia Hard Ciders

Ewing, Brianna Leigh 03 February 2017 (has links)
Though the cidermaking process is very similar to that of winemaking, there is a lack of scientific knowledge as to how orchard management practices and fruit storage affect the quality of the resulting cider. This research examined how both varying harvest maturities and post-harvest storage temperatures and durations in apple cultivars Dabinett, Brown Snout, and York impacted fruit quality as well as the chemistry of the juice and cider. Harvest intervals of two weeks before maturity, at maturity, and 2 weeks after maturity resulted in significant differences in fruit quality and juice chemistry, but few of these differences persisted in cider chemistry. Nonetheless, differences in concentration of some individual polyphenols determined by UPLC-MS were observed in ciders made from fruit harvested at different stages. For example, cider made from optimally mature Dabinett had over 250% the concentration of procyanidin B5 that was found in cider made from fruit harvested earlier or later. The storage treatments also resulted in substantial differences in fruit and juice chemistry, but fewer differences in cider chemistry. As with the harvest maturity experiment, differences in individual polyphenols were detected, with ciders made from cv. York having 20% higher epicatechin concentration when stored for 6 weeks at 1°C rather than 10°C. Finally, the accuracy of the Folin-Ciocalteu (FC) assay, commonly used for quantification of total polyphenols in fruit juices and fermented fruit beverages was critically evaluated. Reducing sugars in the sample matrix did not affect the results of the FC assay, whereas the presence of the amino acid tyrosine resulted in significant overestimation of total polyphenols in fruit juice by the FC assay. / Master of Science in Life Sciences / Cider production and consumption in North America has increased rapidly in recent years. Though cidermaking is in many ways similar to winemaking, there is a lack of scientific knowledge as to how orchard management practices and fruit storage affect the quality of cider. This study examined how varying the harvest date and the ways in which apples are stored after harvest but before cidermaking can affect cider quality. This work was conducted using the apple cultivars Dabinett, Brown Snout, and York. We found that differences in fruit maturity at harvest as well as post-harvest storage parameters impacted fruit, juice and cider quality. However, the differences observed in cider quality as a result of these treatments were much more subtle than the observed differences in fruit and juice quality. This work indicates that in order to accurately assess the impact of orchard management and post-harvest treatments on cider quality, cider should be made and evaluated, rather than assuming that the differences observed in fruit and/or juice will directly translate into cider quality differences.
115

A rice bran polyphenol, cycloartenyl ferulate, triggers caspase-dependent apoptosis in human colon cancer cells. / CUHK electronic theses & dissertations collection

January 2009 (has links)
Findings from this pioneer study demonstrate that CF, which is unique to rice bran oil, is capable of triggering apoptosis in CRC cells at early stages of carcinogenesis. Furthermore, CF enhances TRAIL-induced apoptosis in metastatic CRC cells. This study provides clear evidence that the health-beneficial properties of whole grain consumption are not only limited by the presence of dietary fiber but also other molecules that can either act as a chemopreventive agent to directly induce tumor regression or a sensitizer to enhance TRAIL-induced apoptosis in metastatic cancer cells. / High intake of whole grain food has been suggested as an important factor for reducing the risk of colon cancer, owing to the abundance of indigestible fiber. Rice bran, which is a component of raw rice after removal of starchy endosperm in milling process, has been shown to be a rich source of some health-beneficial compounds for preventing cancer, hyperlipidaemia, fatty liver, hypercalciuria, kidney stones, and heart disease (Jariwalla, 2001). In the present study, proliferation-inhibitory effects of some rice bran polyphenolic compounds were investigated on a panel of human colorectal cancer (CRC) cell lines, including SW480 (stage B), SW620 (stage C) and Colo-201 (stage D) with increasing metastatic potential according to the Dukes' classification system. / Results from the MTT study revealed that, among the polyphenolic compounds tested, cycloartenyl ferulate (CF) showed the most prominent proliferation inhibition on the CRC cells. CF is one of the typical ferulic acid esters of triterpene alcohols present in rice bran oil. The cancer cell proliferation was reduced by 62, 31 and 21% of their control levels after 72 h of 200 muM CF treatment, respectively. CF seemed to possess higher ability to control proliferation of tumor cells at early stages of cancer development. In meanwhile, results from Toxilight study showed that CF had low toxicity on normal colon CCD-18-Co cells. The anticancer activity of CF was further illustrated by its ability to induce significant regression of SW480 xenograft in nude mice. CF was found to induce apoptosis in SW480 cells in vitro. DNA flow cytometric studies demonstrated that CF elevated dose- and time-dependently the sub G1 or apoptotic cells with fragmented DNA. The pro-apoptotic effect of CF was further confirmed using immunoblotting study showing cleavage of poly(ADP-ribose) polymerase (PARP), which is a hallmark feature of apoptosis. Besides, the executioner procaspase-3, -6 and -7 were found to be processed and activated. On the other hand, administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the cells from PARP cleavage, indicating that CF elicited solely caspase-dependent apoptosis. Elevation of death receptors DR4 and DR5 with the CF treatment seems to originate the upstream activation of the initiator procaspase-8 and -10 of the extrinsic apoptosis pathway. Flow cytometric JC-1 studies further demonstrated that CF significantly altered the mitochondrial membrane potential in a dose-dependent manner together with cytochrome c and smac/DIABLO but not AIF release from mitochondria into the cytosol, as well as the activation of procaspase-9 of the intrinsic apoptosis pathway. Depletion of anti-apoptotic Bcl-2 and elevation of pro-apoptotic Bak were observed; meanwhile, Bid was found to be cleaved by caspase-8, so that the death receptor pathway might be exaggerated by the mitochondrial apoptosis pathway. / Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells (Gura, 1997). Result from MTT study illustrated that SW620 was more resistant than SW480 to TRAIL treatment. It is recognized that SW620 is the metastatic form of SW480 derived from the same patient at a later time, so it is important to develop agents that are able to sensitize the cancer cells to TRAIL, or to recover TRAIL sensitivity. We show for the first time that CF sensitizes SW620 cells to TRAIL-induced apoptosis and the mechanisms involved at least elevation of DR4, enhanced activation of caspase-8 and -3, as well as increase in DNA fragmentation. / Kong, Ka Lai. / Adviser: Wong Yum Shing. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 119-136). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
116

Biomarkers of tea and coffee-derived polyphenol exposure in human subjects

Chan, Shin Yee January 2004 (has links)
Tea and coffee are rich in polyphenols with a variety of biological activities. Polyphenols found in tea are predominantly flavonoids, of which up to 15% are present as free or esterified gallic acid. Coffee polyphenols are almost wholly comprised of chlorogenic acids. Many of the demonstrated activities of polyphenols are consistent with favourable effects on the risk of chronic diseases. In investigating the relationships between intake and exposure to such compounds and chronic disease-related endpoints, it is important to be able to identify biomarkers that are specific to the compounds of interest. 4-O-methyl gallic acid (4OMGA) and isoferulic acid have been identified as potential biomarkers of intake and exposure to polyphenols derived from tea and coffee, respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid from chlorogenic acid in coffee. The major objectives of the research which is the subject of this thesis were (1) to establish a dose-response relationship of 24h urinary excretions of 4OMGA and isoferulic acid following ingestions of black tea and coffee of different strengths, and (2) to explore relationships of tea and coffee intake with 24h urinary excretion of 4OMGA and isoferulic acid in human populations. It was found that there was rapid excretion of both 4OMGA and isoferulic acid in the first 6h after tea and coffee ingestion, respectively. Approximately 60 80% of the ingested dose was excreted during the first 6h after ingestion. Urinary excretion of 4OMGA and isoferulic acid was directly related to the dose of tea and coffee, respectively. That is, higher intake resulted in increased urinary excretion of the metabolites. The relationships of 24h urinary excretion of 4OMGA and isoferulic acid with long-term usual (111 participants) and contemporary recorded current (344 participants) tea and coffee intake were assessed. 4OMGA was strongly related to usual (r = 0.50, P < 0.001) and current (r = 0.57, P < 0.001) tea intake. Isoferulic acid was less strongly, but significantly associated with usual (r = 0.26, P = 0.008) and current (r = 0.18, P < 0.001) coffee intake. Overall, the results are consistent with the proposal that 4OMGA is a good biomarker for black tea derived polyphenol intake and exposure, but isoferulic acid may have only limited use as a biomarker for coffee-derived polyphenol exposure.
117

Incidence des conditions d'irrigation et de stockage sur la biosynthèse des caroténoïdes et des polyphénols de la mangue / Incidence conditions of irrigation and storage on carotenoid biosynthesis and mango polyphenols

Rosalie, Rémy 15 June 2015 (has links)
La qualité nutritionnelle de la mangue se construit du champ à la mise sur le marché. Outre le stade de maturité à la récolte, les facteurs environnementaux comme l'irrigation en pré-récolte, ou la température de stockage en post-récolte peuvent avoir une incidence sur la composition du fruit. Les caractéristiques physico-chimiques de la mangue sont également reliées à sa réponse aux espèces réactives d'oxygène (ERO) générées naturellement par la maturation, mais aussi par les contraintes externes (stress abiotiques), avec une incidence directe sur la durée de vie commerciale et la qualité du fruit. Ce travail de thèse a pour objectifs d'évaluer les effets relatifs du stade de récolte, du déficit hydrique ou de la conservation au froid (7 et 12 °C) sur la capacité de réponse de la mangue Cogshall aux ERO et sa capacité de synthèse en caroténoïdes et en polyphénols, composés impliqués dans la qualité nutritionnelle et participant avec l'ascorbate à la régulation du stress oxydatif. L'identification des caroténoïdes et composés phénoliques de la mangue Cogshall, a permis (i) d'approfondir les connaissances existantes sur le cultivar et (ii) de disposer d'un référentiel pour évaluer l'impact des paramètres abiotiques étudiés. La maturation induit un stress oxydatif majeur, mais il est montré que le potentiel de régulation du stress oxydatif lié aux conditions environnementales est partiellement lié au stade de maturité. À la récolte à un stade vert-mature, le déficit hydrique appliqué se traduit par une augmentation du stress oxydatif, avec des teneurs plus élevées en H2O2 et des teneurs en ascorbate plus importantes pour les fruits les plus précoces, une synthèse des teneurs en composés phénoliques marquée. En revanche après maturation, le stress associé à la crise respiratoire estompe les tendances observées quel que soit le stade de récolte. La voie de biosynthèse des caroténoïdes est modulée par le déficit hydrique avec une accumulation marquée d'acide abscissique. Le stockage à basse température pendant 14 jours favorise le stress oxydatif. Après maturation à 20 °C, le stade de récolte et de la température appliquée vont moduler le métabolisme des mangues. Les fruits précoces stockés à basses températures ont les teneurs en caroténoïdes les plus faibles et une capacité de réponse peu développée aux ERO alors que des fruits plus avancés ont un système de défense plus actif et une meilleure accumulation des caroténoïdes. Enfin, les corrélations entre les descripteurs de qualité classiques et la composition des fruits mettent évidence des relations assez robustes entre teneurs en sucres et extrait sec soluble et caroténoïdes majoritaires et angle de teinte, mais montrent aussi des décalages entre caroténoïdes totaux et angle de teinte, entre acidité titrable et acides organiques, quand les fruits sont conservés au froid. / The construction of mango nutritional quality begins in the field and ends on the shelf. In addition to the ripening stage at harvest, environmental factors such as irrigation and post-harvest storage temperature can influence fruit composition. The physico-chemical properties of mango are also related to its response to reactive oxygen species (ROS) that are naturally generated during ripening, as well as to external constraints (abiotic stress), which have a direct impact on shelf life and fruit quality. The aim of this thesis is to evaluate the effects of harvest stage, water deficit and cold storage (7 and 12 °C) on the response ability of Cogshall mango towards ROS and on its ability to synthesize carotenoids and phenolics compounds involved in nutritional quality and that contribute, with ascorbate, to the regulation of oxidative stress. The identification of carotenoids and phenolics from Cogshall mango made it possible to: (i) expand existing knowledge about this cultivar; and (ii) assess reference data in order to evaluate the influence of the abiotic parameters studied.Ripening induces a major oxidative stress, but it was shown that the regulation potential for oxidative stress linked to environmental conditions was, in part, driven by harvest stage. At harvest for the green-mature stage, the water deficit applied resulted in an increase in oxidative stress, with higher H2O2 and ascorbate contents for the earliest fruits, accompanied by a pronounced increase in phenolic content. However, after ripening, the stress linked to the respiration crisis eliminates the trends observed at harvest, regardless of the stage. The carotenoid pathway was modulated by water deficit with a marked accumulation of abscisic acid. Cold storage for 14 days encourages oxidative stress. After ripening at 20 °C, both harvest stage and storage temperature will modulate mango metabolism. Early fruits stored at low temperatures had low carotenoid contents and low ROS scavenging capacities, whereas later fruits had a more active defense system and a better accumulation of carotenoids. Finally, correlations between classic quality descriptors and fruit composition provided strong relationships between sugar contents and dry soluble extract and between major carotenoid contents and hue angle. However, discrepancies were observed between total carotenoids and hue angle and between titratable acidity and organic acid contents when fruits were kept in cold storage.
118

Polyphénols de l'alimentation : extraction, pouvoir antioxydant et interactions avec des ions métalliques / Dietary polyphénols : extraction, antioxidant activity and metal ion interaction

Achat, Sabiha 24 November 2013 (has links)
Les polyphénols sont des métabolites secondaires de végétaux abondants dans l’alimentation. Les extraire dans des conditions efficaces et mieux comprendre leurs propriétés physico-chimiques modulant leurs activités possibles dans le tractus digestif, constituent des enjeux scientifiques importants qui sont à la base de ce travail. La première partie porte sur l’enrichissement de l’huile d’olive en polyphénols par transfert direct de ces derniers des feuilles d’olivier à l’huile, sous irradiation ultrasonore en comparaison avec une macération conventionnelle. Après optimisation des paramètres d’extraction, la technique sous-ultrason à 16°C s’est révélée plus efficace que le procédé conventionnel du laboratoire (réacteur de 3 L) à l’échelle pilote industriel (réacteur de 30L). Dans la seconde partie, la réactivité de polyphénols communs et représentatifs des principales classes(rutine, quercétine, catéchine, acide chlorogénique et phénols de l’olive) avec le radical DPPH• et les ions de métaux de transition d’intérêt biologique(FeII, FeIII, CuI, CuII), a été étudiée par spectroscopie UV-visible (études cinétiques), par CLUP-SM (analyse de produits d’oxydation) et au moyen des tests colorimétriques permettant de préciser l’état redox des ions métalliques. L’étude de l’activité antiradicalaire (test DPPH•) en milieu micellaire aqueux a confirmé la capacité antioxydante des polyphénols sélectionnés en présence et en absence de la protéine sérum albumine bovine (SAB) etd’un modèle d’amidon (&#946;-cyclodextrine). L’étude de la capacité des composés phénoliques à complexer les ions métalliques, en solution faiblement acide (pH= 5-6), a suggéré que les flavonols et acides hydroxycinnamiques sont susceptibles de complexer Fe III dès le compartimen tgastrique quand le pH est faiblement acide (1-2 h après le repas). Par contre, l’interaction avec Fe II et les ions du cuivre est probablement négligeable.L’interaction Fe III – polyphénol conduit à des complexes stables (sans oxydation notable du polyphénol) mais peut être inhibée par les interactionspolyphénol-protéine / Polyphénols are plant secondary metabolites which are abundant in the diet. Their extraction using efficient processes and a better understanding of their physico-chemical properties that modulate their possible activities in the gastric tract are important scientific goals which underline this work. The first part deals with the direct enrichment of olive oil in polyphénols of olive leaves under ultrasonic irradiation in comparison with conventional maceration. After optimization of extraction parameters, the ultrasound-assisted process came up as more efficient than the conventional method at laboratory (reactor 3 L) to industrial pilot scale (reactor 30L). In the second part, the reactivity of some polyphenols, both common an representative ot the main classes (rutin, quercetin, catechin, chlorogenic acid and olive phenols) with DPPH radical and transition metal ions of biological interest (FeII, FeIII, CuI, CUII) was studied by UV-visible spectroscopy (kinetic studies), UPLC-MS (analysis of oxidation products) and via colorimetric tests for the determination of the redox state of the metal ions.The study of the antiradial activity (DPPH test) in aqueous micellar medium confirmed the antioxidant capacity of selected polyphenols in the presence and absence of bovine serum albumin (BSA) protein and a starch model (b-cyclodextrin). The study of the ability of phenolic compounds to bind metal ions in weakly acidic solution(pH=5-6), suggested that flavonols and hydroxycinnamic acids are able to complex FeIII from the gastric compartment when pH is slightly acid (1-2 h after the meal). However, interaction with FeII and copper ions is probably negligible. Interaction FeIII-polyphenol leads to stable complexes (without significant oxidation ot he polyphenol), but can be inhibited by the polyphenol-protein interactions
119

FOOD MATERIALS SCIENCE: EFFECTS OF POLYPHENOLS ON SUCROSE CRYSTALLIZATION AND CHARACTERIZATION AND CREATION OF ALTERNATIVE SALTS OF THIAMINE

Collin J. Felten (5930618) 17 January 2019 (has links)
<div> <p>Proper understanding of materials science is critical in understanding the functionality of ingredients in food products, as well as their behavior in these products over time. Amorphous materials are metastable, eventually rearranging to the thermodynamically stable crystalline state. Amorphous materials have properties which are beneficial in some food products: they are softer in texture and dissolve more rapidly. The amorphous state of sucrose might provide an increase in quality in applications like powdered beverages where rapid dissolution is preferred. A number of classes of compounds have been shown to delay the crystallization of amorphous sucrose; however, polyphenols, particularly their glycosylated forms, have been little explored. Glycosylated polyphenols contain two distinct structural regions: a more hydrophilic sugar unit(s) and a more hydrophobic polyphenol backbone. While the sugar unit should be able to easily associate with sucrose molecules, the polyphenolic backbone may not and might provide hindrance to crystal nucleation and growth.</p> <p> </p> <p> Thiamine is an essential nutrient that is found naturally in foods such as whole grains and pork. The processing of grains removes nearly the entirety of the natural thiamine content; thus, foods are often enriched with synthetic thiamine. Two salts of thiamine are used commercially: thiamine mononitrate and thiamine chloride hydrochloride. The two forms have specific applications driven by their specific properties, specifically their aqueous solubility and hygroscopicity. While these two salts provide adequate functionality, it is possible new salts may have properties beneficial in certain food applications. A method making use of silver nitrate was developed to produce new salt forms. An intermediate in this reaction, TCl·H<sub>2</sub>O, was characterized including measurements of stability in aqueous solutions and solid state properties.</p> </div> <br>
120

Evaluation et caractérisation des effets anticancéreux de fruits rouges riches en polyphenols dans des modèles de cancer colorectal et de leucémie lymphoïde chronique / Anti-cancer properties of berries rich in polyphenols in colorectral cancer models and chronic lymphocytic leukama : evaluation and characterization of the cellular and the molecular mechanisms

Dandache, Israa 25 September 2013 (has links)
L’évaluation de l’effet cytotoxique de différents jus de fruits naturellement riches en polyphénols vis-à-vis de quatre lignées de cancer colorectal a montré que le jus de la canneberge est particulièrement actif. En effet, les polyphénols de la canneberge induisent l’apoptose associée à une surexpression des deux facteurs de transcription pro-apoptotiques p73 et FOXO3a. Cette mort programmée est aussi associée à une diminution de l’expression de SIRT1 le déacétylateur de protéines non histone telles que p73, KU70, ou FOXO. D’autres événements précoces comme la production de ROS et les dommages à l’ADN connus pour réguler l’expression de SIRT1 ont été confirmés. Une deuxième étude avait pour objectif de valider le potentiel anticancéreux in vivo chez la souris Balb/C injectée de cellules d’adénocarcinome colique murin. Pour cela nous avons choisi le jus d’aronie noire qui a montré in vitro un profil de cytotoxicité intéressant. L’analyse des tumeurs a montré que l’administration de jus d’aronie entraine une réduction de la prolifération des cellules tumorales. Enfin, l’augmentation significative de la mobilité de LC3 suggère l’activation d’une mort cellulaire autophagique. Afin d’évaluer l’utilisation clinique des polyphénols, nous avons évalué les effets cytotoxiques des polyphénols de myrtille sur des lymphocytes, de patients atteints de LLC. Nos résultats montrent que l’extrait polyphénolique induit une apoptose dépendante du stress oxydant et impliquant aussi des protéines pro-apoptotiques dans des cellules de patients atteints de LLC mais pas dans les cellules de sujets sains. / The evaluation of the cytotoxic effect of different fruit juices, naturally rich in polyphenols, on four different colorectal cancer cell lines proved that cranberry juice was the most active. Indeed, cranberry polyphenols induce apoptosis associated with the overexpression of two important proapoptotic transcription factors, p73 and FOXO3a on one hand. Furthermore, it has been also correlated with a decrease in the expression of SIRT1, the deacetylase of several non-histone proteins such as p73, KU70 and FOXO. Other early events such as ROS production and DNA damage, which are known to regulate the expression of SIRT1 were confirmed. The second study aims at validating the potential anticancer effects in an in vivo model of colorectal cancer in BALB/c mice injected subcutaneously of murine colon adenocarcinoma cells. Accordingly, we chose the black chokeberry juice, which showed an interesting cytotoxic profile in vitro. The analysis of tumors demonstrated that the administration of chokeberry juice leads to a reduction in tumor cell proliferation. Finally, the significant increase in the mobility of LC3 suggests the activation of autophagic cell death. To validate the clinical use of polyphenols, we evaluated the cytotoxic effects of blueberry polyphenols on lymphocytes of CLL patients. Our results show that the polyphenolic extract induces an oxidative stress-dependent apoptosis that involve various pro-apoptotic proteins in cells of patients with CLL but not in healthy subjects.

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