Tesis sobre el tema "Métabolisme des xénobiotiques/odorants"
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Mérignac-Lacombe, Jeanne. "Approches innovantes dans la caractérisation des enzymes du métabolisme des xénobiotiques dans les muqueuses nasales : du modèle animal à l’ingénierie tissulaire". Electronic Thesis or Diss., Bourgogne Franche-Comté, 2024. http://www.theses.fr/2024UBFCI003.
Texto completoOur sensitive olfaction relies on Xenobiotic Metabolizing Enzymes (XMEs) that protect the nasal tissue from potentially harmful volatile compounds, but also quickly terminate the olfactory signal to prepare olfactory receptors to detect new odorant stimuli. Some of them also generate metabolites that participate in the odorant signal, hence their other name Odorant Metabolizing Enzymes (OMEs). The objective of this thesis was to study the nasal XMEs using two innovative models that aim to comply as much as possible with the 3R principles (Replacement, Reduction, and Refinement of animal experiments). While rat olfactory explants showed some limitations in investigating XME gene expression, human nasal respiratory mucosa tissue models were promising in vitro tools for the odorant metabolism field. These models express around 80 XME isoforms and efflux transporters. Selected XME genes were not regulated by the compounds chosen for the thesis, however, they were able to metabolize odorants, such as benzaldehyde and 3,4-hexanedione. Overall, protocols were created and adapted to use tissue models to study the implication of the respiratory epithelium in odorant metabolism in humans. This work provides novel knowledge on the involvement of the human respiratory tissue in odorant metabolism and contributes to the reduction of animal experiments
Minn, Anne-Laure. "Caractérisation des enzymes et des transporteurs impliqués dans le métabolisme des xénobiotiques dans les tissus olfactifs". Dijon, 2005. http://www.theses.fr/2005DIJOPE01.
Texto completoRobert-Hazotte, Aline. "Impact du métabolisme des molécules odorantes sur la perception olfactive chez l'Homme". Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCK073.
Texto completoThe sense of smell permits the perception of volatile substances commonly known as odors. This sense plays an important role in the feeding and wellness of individuals because it involves exchanges with their environment (search for food or partners, predators detection…). The efficiency of the olfactory system mainly relies on its sensitivity depending on the odorant affinity for their olfactory receptors but also on an enzymatic clearance mechanism of odorants which involves the Odorant metabolizing Enzymes (OME) to avoid the saturation of the receptors. Recent studies have shown that the biotransformation of odorants by EMO, in the olfactory epithelium, participates in the olfactory perception. Indeed, OME catalyse the deactivation of the odorants and their subsequent elimination which led to the termination of the olfactory signal. In this context, this work aims to provide a better understanding of the enzymatic mechanisms of the OME in mammal olfactory perception and to study more specifically these mechanisms in human.The first axis of this work, based on physicochemical analysis, has consisted to develop an innovative proton transfer reaction mass spectrometry technique (PTR-MS) to allow the analysis in real time of the odorants biotransformation by OME. This technique was first applied ex vivo using rats and rabbits olfactory epithelium and olfactory mucus but also in vivo directly inside the human nasal cavity. Thus, we have demonstrated that the olfactory biotransformation of odorants catalyzed by different enzymes like glutathione transferases, carboxylesterases and dicarbonyl xylulose reductases (DCXR), is a very fast mechanism (few milliseconds). This very high velocity is perfectly consistent with the physiological dynamics of the olfactory process. Moreover, PTR-MS analyzes revealed that the odorants biotransformation could produce volatile metabolites with odorous properties which could participate in the global olfactory perception by interacting also with olfactory receptors. These various metabolites have been formally identified by a gas chromatography-mass spectrometry technique (GC-MS).The second axis, based on psychophysical method, evaluated the impact of the odorant metabolism in the human olfactory perception. For this purpose, an original approach recently developed in the lab, consisting of the modulation of the olfactory perception through a competition between odorants metabolized by the same EMO was transposed from the rabbit model to the human. The metabolic competition between several diketones toward DCXR was first demonstrated by biochemical analysis using the corresponding human recombinant enzyme. Then, an olfactometric study carried out on a 40 subjects panel demonstrated that this competition mechanism between odorants induces modulations of the biotransformation of these molecules and thus leads to modifications of their relative bioavailability and in fine of their perception. These new and significant results demonstrate that modulations impacting odorants metabolism leads immediately to changes in their olfactory perception. This thesis highlights on the function of EMO in mammals and reveals for the first time in human a significant role of the odorant metabolism in olfactory perception
Thiebaud, Nicolas. "Caractérisation des enzymes du métabolisme des xénobiotiques olfactives chez le rat : régulation et rôle dans la détection périphérique des molécules odorantes". Thesis, Dijon, 2010. http://www.theses.fr/2010DIJOS024.
Texto completoXenobiotic metabolizing enzymes (XMEs) play a central role in the biotransformation and the elimination of foreign compounds reaching the body. Organized as a biotransformation network, these enzymes catalyze various reactions (oxidations, conjugations …) in order to increase the water solubility of compounds. XMEs are highly expressed in the mammalian olfactory epithelium and in vitro studies showed that they have important activities. Besides a role in the metabolism of toxic compounds, a role in the peripheral regulation of the olfactory process has been hypothesized. XMEs could contribute to maintain the sensibility of the olfactory system, by eliminating or inactivating odorant molecules present in the perireceptor space. However, scientific proofs of such a role are still limited. In a first study, we demonstrated that olfactory XMEs can be modulated by chemical treatments identified to induce the enzyme expression in the liver (dexamethasone, Aroclor …). The intensities of the effects were lower in the OM than in the liver. Dexamethasone, a synthetic glucocorticoid, was found to increase significantly the expression of several enzymes and transporters in the olfactory mucosa. This study suggests that the expression of olfactory XME is controlled by tissue-specific mechanisms. In the second part, the metabolism of some odorant molecules was studied in vitro. We observed that the olfactory mucosa of rats possesses a high metabolic capacity and catalyses the formation of hydroxylated metabolites. Finally, the consequences of this metabolism were evaluated by recording electro-olfactograms (EOG) from the olfactory mucosa of rats. We showed that, at same concentrations, amplitudes of EOG signals generated by the metabolites were lower than those elicited by the parent molecules. Moreover, the perfusion of the mucosa with specific inhibitors of cytochromes P450 or carboxylesterases induced a significant modification of EOG signals. These studies demonstrate that the biotransformation of odorant molecules have an impact on the olfactory signal. Taken together, these studies support the hypothesis that XME are involved in the first stage of the olfactory perception. These enzymes could catalyze the biotransformation of odorant molecules in order to avoid the saturation of the olfactory system
Schoumacker, Rachel. "Perception du gras : variabilité interindividuelle et origine". Thesis, Dijon, 2016. http://www.theses.fr/2016DIJOS030/document.
Texto completoTo reduce the fat content in food products as recommended by the National Nutrition and Health Plan, it is necessary to understand the fat perception mechanisms. In this context, this thesis work aimed to contribute to the understanding of fat perception through the study of interindividual variability in fat perception and the research of its origin.For this purpose, a multidisciplinary approach combining physico-chemistry of “fatty” aroma molecules, subjects’ oral physiology, food oral processing and sensory perception during food consumption has been established. A particular focus has been done on the olfactory component of fat perception, especially on the potential contribution of the metabolites produced in the human nasal cavity from odorous volatile compounds.This work shows that reducing fat content in cottage cheese decreases the perception of the cream aroma, increases bitterness and astringency and decreases the perceived greasy film. The results confirmed the multidimensional nature of fat perception. This work also shows that fat perception is related to the lipid content of the mouth coating as well as the aroma compounds composition of the food matrix.It highlights three groups of subjects with significant difference in fat sensitivity. These groups also differ in several physiological and anatomical parameters which can impact tactile, taste and smell sensations and therefore potentially fat perception. Finally, this work proves the existence in the human olfactory mucosa of enzymes capable of metabolizing odorous compounds into volatile metabolites. These metabolites proved to be themselves odorants could be involved in fat perception or its modulation
Souhaili-El, Amri Hajar. "Albendazole : métabolisme et régulation des enzymes hépatiques du métabolisme des xénobiotiques". Nancy 1, 1988. http://www.theses.fr/1988NAN10122.
Texto completoLakehal, Fatima. "Métabolisme et toxicité des xénobiotiques dans l'épithélium biliaire". Paris 5, 2000. http://www.theses.fr/2000PA05N021.
Texto completoLe, Daré Brendan. "Xénobiotiques hépatotoxiques : études de métabolisme et mécanismes d’action". Thesis, Rennes 1, 2021. http://www.theses.fr/2021REN1B005.
Texto completoXenobiotic-induced hepatotoxicity is an extremely rich subject, given the multiple mechanisms and actors involved. This translational work aims to improve ethanol and amanitins (powerful fungal toxins) hepatotoxic mechanisms understanding, in order to provide new elements to optimize the therapeutic management of intoxicated patients. In a first step, we provide additional elements of understanding on macrophages response mechanisms to ethanol. These xenobiotic-cell interactions, shown through the P2X7 receptor induction example, seem to contribute in alcoholic liver damage severity, and testify to the macrophages plasticity in pathological situations. These results suggest in particular the interest of P2X7 receptor antagonist’s development in the treatment of alcoholism. In a second step, we are applied molecular networking, which allows the visualization of complex data acquired by LC-MS/MS, to xenobiotic metabolism study. The acebutolol metabolism example, in the context of voluntary drug intoxication on the one hand, and the in vitro quetiapine metabolism study on the other hand, have provided consistent evidence concerning molecular network interest in this context. In a third and final step, the molecular network application allowed us to rule out the hypothesis of an in vivo and in vitro amanitins metabolism. Moreover, our results show that the hepatocyte-like cellular model of differentiated HepaRG is a relevant model in amanitins study, and show the mitochondrial ROS production implication in these substances toxicity
Chraibi-Ben, Moubarik Soumaya. "Contribution à l'étude de l'influence de chaines ramifiées courtes sur le métabolisme des xenobiotiques". Rouen, 1999. http://www.theses.fr/1999ROUEM007.
Texto completoRésume en anglais
Waziers, Isabelle de. "Le Métabolisme intestinal des xénobiotiques et la cancérogénèse colorectale". Paris 5, 1994. http://www.theses.fr/1993PA05P602.
Texto completoVérité, Philippe. "Etude par CPG-SM de métabolites formés à partir de trois familles de xénobiotiques par l'animal entier ou par des hépatocytes isolés". Rouen, 1992. http://www.theses.fr/1992ROUEO1NR.
Texto completoRibera, Daniel. "Métabolisme oxydatif chez la moule : péroxydation lipidique et biotransformation des xénobiotiques". Bordeaux 1, 1990. http://www.theses.fr/1990BOR10553.
Texto completoLegendre, Arièle. "Rôle des enzymes du métabolisme des xénobiotiques dans les processus chimiosensoriels : contribution de deux modèles de perception phéromonale". Dijon, 2009. http://www.theses.fr/2009DIJOS063.
Texto completoIndividuals can detect stimuli in their environment (food, sexual partner. . . ) by chemoperception process. To be efficient, these process need to be sensitive, discriminant and able to avoid saturation of the receptors. In the perireceptor environment, the xenobiotic metabolizing enzymes (XME), involved in detoxification by catalyzing the biotransformation of xenobiotics, could have a key role in the modification or the termination of the sensory signal. To study the involvement of XME in chemosensory process, and especially in the phéromonal perception, two complementary approaches have been used. The first one consisted in studying the olfactory metabolism of the mammary pheromone in the rabbit; the second consisted in studying the functional involvement of different XME genes in the genetic model drosophila. The most important results are : (i) In the rabbit, there is an in vitro glutathione-dependent metabolism of the mammary pheromone which varies according to age and the type of tissue. These variations are also found for some XME genes. Ex vivo, the global metabolism of the olfactory mucosa toward the mammary pheromone is affected by a modulator of glutathione-transferases activity or by a pre-exposition to the mammary pheromone. (ii) In the drosophila, we used transgenic tools to modulate expression of different XME (cytochromes P450, UDP-glycosyltransferase), in particular in sensory appendages. We demonstrated the involvement of XME in the discrimination of sex pheromones. As a whole, this work provides original physiological data supporting the involvement of XME in the metabolism or perception of pheromones
Smyej, Mohamed. "Contribution à l'optimisation de l'autoradiographie macroscopique dans les études de distribution de xénobiotiques". Toulouse, INPT, 1993. http://www.theses.fr/1993INPT025A.
Texto completoNasraoui, Ahmed. "Effets de l'oxygène normobare sur les enzymes hépatiques du métabolisme des xénobiotiques". Paris 7, 1986. http://www.theses.fr/1986PA077225.
Texto completoLacombe, Olivier. "L'absorption intestinale des xénobiotiques : caractérisation chez le rat". Toulouse 3, 2005. http://www.theses.fr/2005TOU30045.
Texto completoThe intestinal absorption and metabolism of drugs has been studied in the rat. Using the everted gut sac, a complimentary method to the Caco-2 system, a correlation (r2=0. 91) between the fraction absorbed (Fabs) in vivo and the apparent permeability (Papp) of molecules absorbed by passive diffusion was observed. The Papp of most compounds was 2-3 times lower in the duodenum and ileum than in the jejunum, with the exception of digoxin, which showed a decreased absorption down the intestine, consistent with an increasing activity of P-glycoprotein (P-gp). Five CYP450 activities were characterised using an optimised preparation of intestinal microsomes, and a comparison of the metabolic activities between the microsomes and everted sacs highlighted the importance of the transcellular absorption. The specific activities of hepatic CYP450 enzymes were higher than those of the small intestine. More than 80% of the intestinal activity was located in the upper half of the jejunum
Debbasch, Anne. "Modèle "in vitro" d'étude de la glucuroconjugaison des xénobiotiques : application au métabolisme de l'UP 26-70". Paris 5, 1991. http://www.theses.fr/1991PA05P137.
Texto completoLançon, Allan. "Transport et métabolisme du trans-resvératrol dans la lignée cellulaire d'hépatoblastome humain HepG2". Dijon, 2006. http://www.theses.fr/2006DIJOS024.
Texto completoTrans-resveratrol, a natural polyphenol abundant in red wine could fight against numerous diseases such as cancer. To consider a therapeutic use of resveratrol, its bioavailability at hepatic level was studied with HepG2 cell line by using fluorescence microscopy, radiolabelled resveratrol transport determination and analysis of cell culture media by HPLC and mass spectrometry. It was shown that resveratrol was rapidly taken up by cells following both an active transport process and a passive transport before its modification in mono- and disulfated metabolites that were finally excreted by MRPs transporters. At the same time on this cell line, transport and antiproliferative properties of resveratrol derivatives were compared. Finally, the endocrine disrupting effect of resveratrol and other estrogenomimetics (genistein and bisphenol A) was studied at the estradiol transport level
Daverat, Florence. "Influence des xénobiotiques sur les structures et les fonctions mitochondriales". Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P056.
Texto completoPrévost, Colette. "Influence des régimes lipidiques sur les phénomènes d'induction médicamenteuse : étude sur foie isolé, perfusé de rat". Dijon, 1985. http://www.theses.fr/1985DIJOS011.
Texto completoQuantin, Paul. "Étude du métabolisme cutané des xénobiotiques dans un contexte d’évaluation du risque pour l’Homme". Thesis, Compiègne, 2018. http://www.theses.fr/2018COMP2404.
Texto completoThe assessment of the fate of a substance applied to the skin, or dermatokinetics, is a crucial step in describing the exposure of the molecule in an organism. For toxicological risk assessment of cosmetic products, this mechanism should be evaluated to reduce the risk of developing dermal side effects. It is increasingly recognized that skin metabolism can play a key role in the biotransformation of molecules capable to cross the stratum corneum. Although basal activity is very low, often close to detection limits, some enzymes can be induced by various compounds. The objectives of this thesis are twofold: the fundamental study of the induction regulation of metabolism and the development of a model applied to the simulation of skin metabolism. From the various skin models available for research, induction studies have been carried out at several scales. In vitro, the use of molecular biology methods allowed to study the mechanisms of transcriptional induction of cytochromes-P450 in the skin. Transcriptomic induction results were confirmed by enzymatic activity studies. The work was continued by in vivo studies to establish a physiological mechanism for induction of skin enzymes expression after a systemic exposure to an inducing agent. In the second part of the project, a bioreactor was designed to simulate absorption and metabolism in order to establish a predictive model of dermatokinetic. The experiments are concentrated on the development of an enzymatic chip using a layer-by-layer self-assembly of membrane fractions, expressing enzymes of interest and a polymer. Physicochemical methods were used to characterize the functionalized surfaces. A "proof of concept" study of the bioreactor in full configuration concluded the experimental work. The knowledge and expertise acquired in this project can be used to better understand the impact of cutaneous metabolism on the bioavailability and consequences for human risk assessment
Boutet, Isabelle. "Réponses aux stress induits par les xénobiotiques chez l'huître creuse Crassostrea gigas : approches cellulaire et moléculaire". Brest, 2003. http://www.theses.fr/2003BRES2018.
Texto completoExposure to xenobiotics (human origin) constitutes a major physiological stress in organisms inhabiting marine ecosystems. Sedentary animals such as the oyster Crassotrea giga are more exposed to these sources of stress and have developed some resistance mechanisms. The stress response concept could be defined as the synthesis of proteins as a response to environmental changes (contaminant exposure, heat shock, anoxia. . . ). The main objectives of this work were the understanding of mechanisms used by oyster in response to anthropogenic stress sources (metals and hydrocarbons, particularly) and the development of genetic and cellular indicators of these stress. First, we developed an antibody for metallothioneins (MTs) (metal detoxification) in order to quantify and localised MTs in tissues of oysters exposed to metals. The results indicated that MT quantify increased during experiments and that MTs are localised in gills and digestive gland epithelium and in ovocyte nucleus. Then, we sequenced 2 genes encoding the inducible (HSP70) and the constitutive (HSC70) forms of the Heat Shock Proteins 70. The polymorphism of HSC70 was analysed and revealed a potential selection by metal. The uncertain number of gene copies and the high number of profiles make the analysis difficult. An antibody for HSP70 was developed and the quantification of the protein revealed a decrease in metal-exposed oysters and an increase in hydrocarbon exposed oyster. HSP70 were localised in epithelium, as shown for MTs. Finally, we examined hydrocarbon-detoxification processes by using suppression subtractive hybridisation method. A number of 252 hydrocarbon-regulated genes were detected and 10 amongst them were directly involved in hydrocarbon biotransformation. An analysis of their mRNA expression indicated their potential use as a marker of hydrocarbon contamination. Complementary work conducted on these marker could serve to the development of accurate and fast tools, such as DNA ship, allowing gene expression analysis in response to various stress or physiological changes in oysters
Anthelme, Bernard. "Mécanismes intracellulaires mis en jeu dans le métabolisme des phénols et du benzo(a)pyrène : approche microspectrofluorimétrique". Perpignan, 1989. http://www.theses.fr/1989PERP0057.
Texto completoRouguieg-Malki, Koukeb. "Etudes des relations génotype-phénotype des enzymes du métabolisme et des transporteurs d'efflux des xénobiotiques". Limoges, 2010. https://aurore.unilim.fr/theses/nxfile/default/1c8b244e-e3b4-4e4e-a896-2784dba945cb/blobholder:0/2010LIMO310E.pdf.
Texto completoIn the body, the detoxification of xenobiotics (drugs, carcinogens. . . ) involves phase I and II biotransformation enzymes, as well as efflux transporters. We investigated several aspects of the genotype-phenotype relationships of these enzymes and transporters. We showed that the functional polymorphism of cytochrome P450 (CYP) 3A5 (Phase I enzyme), CYP3A5*3 has no influence on the metabolism of the immunosuppressive drug everolimus, in vitro and among 30 kidney transplant patients. We found that the UDP-glucuronosyltransferase (UGT; phase II enzymes) isoforms involved in the metabolism of buprenorphine (opioid replacement therapy) are the UGT 1A1, 1A3 and 2B7. Moreover, we showed in vitro that among UGT1A1*1/*1 genotype carriers, the presence of at least one UGT2B7 G-842A mutated allele was associated with an increased buprenorphine glucuronidation activity. We developed an in vitro « cocktail » method to evaluate the hepatic activity of five UGTs (1A1, 1A4, 1A6, 1A9 and 2B7). This approach consists in the simultaneous estimation of several enzyme activities after incubation of a mixture of selective substrates with human liver microsomes. We used this method to evaluate the inhibitory effect of buprenorphine on these five UGT activities. Finally, we retrospectively investigated the association between common polymorphisms in the genes coding UGT 1A6, 1A7, 1A8, 1A9 and 2B7 and efflux transporters (MDR1 and MRP2) and colorectal cancer (CRC) by comparing cases (colorectal cancer patients) to two control groups (patients suffering from kidney cancer or healthy volunteers). Three polymorphisms of the MDR1/ABCB1 gene (C1236T, G2677T and C3435T) as well as its triple mutant haplotype were significantly related to a very low incidence of CRC. We also found for the first time an association between this cancer and MRP2/ABCC2 gene haplotypes. These investigations provide knowledge about polymorphisms impact on drug metabolism and potential involvement in CRC
Boulenc, Xavier. "Utilisation de la lignée cellulaire humaine colique Caco-2 pour l'étude du métabolisme et de l'absorption des xénobiotiques au niveau intestinal". Montpellier 2, 1994. http://www.theses.fr/1994MON20133.
Texto completoBengone-Ndong, Toussaint. "Contribution à l'étude des conséquences du gavage de canards sur le devenir des xénobiotiques". Toulouse, INPT, 1996. http://www.theses.fr/1996INPT005A.
Texto completoKlieber, Sylvie. "Optimisation du modèle des hépatocytes humains en culture primaire pour l'étude de la métabolisation des xénobiotiques". Montpellier 1, 2007. http://www.theses.fr/2007MON1T030.
Texto completoHugonnard, Marine. "Les monooxygènases à Flavine chez le rat : identification et caractérisation d'un polymorphisme du gène FMO2 : étude de la distribution tissulaire et des propriétés catalytiques de la FMO5". Lyon 1, 2005. http://www.theses.fr/2005LYO10277.
Texto completoDenizot, Claire. "Validation de cultures de cellules endothéliales cérébrovasculaires comme modèle d'étude des conséquences oxydatives du métabolisme de xénobiotiques". Nancy 1, 1998. http://www.theses.fr/1998NAN10352.
Texto completoSaunier, Elise. "Impact des xénobiotiques sur la progression tumorale des cellules cancéreuses humaines". Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB148.
Texto completoThe impact of the environment in the development of several human diseases is well established but difficult to evaluate. Humans are chronically exposed to xenobiotics mixture - foreign chemicals substances which are not normally present within the organism – with different nature, concentration and interactions leading to deleterious or beneficial effects on human health. Among these xenobiotics, environmental pollutants play a significant role in the development of some cancers. On the contrary, a natural molecule like resveratrol has anti-cancer properties. During carcinogenesis, tumor cells acquire a reversible metabolic phenotype characterized by a high glycolysis and a massive lactate production with or without oxygen (Warburg effect). The flexibility of the metabolism allows cancer cells to provide sufficient levels of energy, metabolites and cofactors to maintain their tumor phenotype in a fluctuating microenvironment. In this study, the effects of several xenobiotics alone or in a mixture were assessed on human cancer cell progression. In the first part, the effects of 2 persistent organic pollutants acting by different signaling pathways, tetrachlorodibenzo-para-dioxin (TCDD) and a-endosulfan, an organochlorine pesticide, were studied alone or in a mixture, on human colonic cancer cells (Caco2) progression. We have shown that TCDD (25 nM) and a-endosulfan (10µM) decrease the oxidative capacity of tumor cells. This effect is more pronounced when cells are exposed to the mixture, suggesting a synergistic effect. These alterations are associated with a drastic decrease in mitochondrial respiration, correlated with a strong reduction in the activity of the mitochondrial respiratory chain complex I. These observations are in part linked to a decrease of NDUFS3 gene expression, one of the subunit of the complex I. We have also found that the dysregulation of tumor cell metabolism was associated with an epithelial-mesenchymal transition (EMT). Our data show that pollutants strengthen the Warburg effect associated with an EMT, which suggests that the pollutants affect the progression of the tumor phenotype. The signaling pathways involved in these observations are under investigation. In the second part, we assessed the effects of resveratrol (RSV), a natural compound present among other in wine, on cancer cell progression. This polyphenol has been widely described for its benefits on cancer and its ability to mimic caloric restriction. We have shown that the RSV, with a close concentration of serum doses measured in humans (10 µM), decreases cell proliferation without modulate cell viability. RSV redirects the energy metabolism of tumor cells by increasing their oxidative capacity, decreasing their glycolytic capacity and reducing the activity of the pentose phosphate pathway. We have identified the complex pyruvate dehydrogenase as a target of the RSV and highlighted that the calcium is involved in the regulation of PDH activity. We have also shown that the RSV induces its metabolic effects in part through CamKKß/AMPK signaling pathway. These results demonstrate that the xenobiotics can modulate tumor phenotype, and tumor metabolism, because of its extreme flexibility, is a major target of these modulations
Claud, Philippe. "Implication de la Semicarbazide-Sensitive-Amine-Oxydase dans le métabolisme d'une nouvelle entité chimique". Dijon, 2001. http://www.theses.fr/2001DIJOPE05.
Texto completoMassart, Julie. "Effets hépatiques et métaboliques de la pentoxifylline chez la souris ob/ob : un exemple d'interaction entre xénobiotiques et obésité". Paris 5, 2010. http://www.theses.fr/2010PA05P643.
Texto completoKaddouri, Mohammed. "Évolution ontogénique de l'enzymologie hépatique de biotransformation chez l'ovin femelle de race Lacaune : étude de xénobiotes et de la progestérone". Toulouse, INPT, 1991. http://www.theses.fr/1991INPT016A.
Texto completoEllero, Sandrine. "Conséquences Moléculaires de l'Exposition du Tissu Adipeux Humain à des Xénobiotiques Environnementaux". Phd thesis, AgroParisTech, 2010. http://pastel.archives-ouvertes.fr/pastel-00610847.
Texto completoClair, Philippe. "Expression de cytochromes P-450, de la NADPH cytochrome P-450 réductase et de monooxygénases à flavine par baculovirus recombinants : Une contribution à l'étude du métabolisme des xénobiotiques chez l'homme". Montpellier 2, 1993. http://www.theses.fr/1993MON20248.
Texto completoRat, Emmanuel. "Variabilité d'origine génétique de la biotransformation des xénobiotiques et des composés endogènes : application à la détoxication des cyanures et au métabolisme de l'acide rétinoïque". Lille 2, 2006. http://www.theses.fr/2006LIL2S069.
Texto completoPerrin, Rachel. "Caractérisation de deux sous-familles d'isoenzymes du cytochrome p450 impliquées dans le métabolisme des xénobiotiques dans le cerveau". Nancy 1, 1991. http://www.theses.fr/1991NAN10462.
Texto completoSaves, Isabelle. "Evolution de la béta-lactamase TEM-1". Toulouse 3, 1995. http://www.theses.fr/1995TOU30206.
Texto completoBret-Bennis, Lydie. "ADN extracellulaire et nucléosomes : marqueurs de cytotoxicité". Toulouse 3, 1992. http://www.theses.fr/1992TOU30135.
Texto completoHirel, Béatrice. "Kératinocytes humains adultes en culture : expression et modulation des marqueurs de différenciation et des enzymes de biotransformation des xénobiotiques". Rennes 1, 1994. http://www.theses.fr/1994REN1B026.
Texto completoRoy, Isabelle. "Contribution à la mise en place d'un modèle "in vitro" prédictif de l'absorption et du métabolisme intestinal". Paris 5, 1994. http://www.theses.fr/1994PA05P159.
Texto completoDelannée, Victorien. "Intégrer les échelles moléculaires et cellulaires dans l'inférence de réseaux métaboliques : application aux xénobiotiques". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S058/document.
Texto completoPredicting, modelling and analysing the metabolism of xenobiotics, substances foreign to an organism, using computer methods, has been a major challenge for the scientific community for many years. This thesis aims to implement multiscale computing methods for predicting and analyzing the metabolism of xenobiotics. A first focus of this study was on the construction and automatic de novo annotation of metabolic graphs combining high sensitivity and precision. These graphs thus provide the prediction of the metabolism of xenobiotics in humans, as well as the genotoxicity of the molecules and atoms that make up xenobiotics. Then, the work focused on the implementation of a dynamic mathematical model modelling enzymatic competition effects through the development of a methodology allowing the exploitation of limited biological data while limiting inherent biases
Moss, Éric. "Etude in situ par RMN HRMAS sur des épidermes reconstruits du métabolisme et de la réactivité de xénobiotiques allergisants". Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAF003/document.
Texto completoContact dermatitis is a skin pathology particularly prevalent in industrialized countries. No therapy currently exists and only complete avoidance of the particular allergen can prevent an allergic reaction. Historically, the assessment of skin sensitisation potential of molecules placed on the market was always carried out by animal testing. However, the scope of this testing method is now limited by the new European cosmetics legislation. In this way, the development of alternative methods, not based on animal experimentation, become an important issue. Contact dermatitis results of a chemical key step: the formation of an antigenic complex allergen-protein complexe able to activate the cutaneous immune system. The aim of this PhD work was to study the in situ behaviour of allergens in reconstructed human epidermis (SkinEthic® model). By using an appropriate non-invasive analysis technique, HR-MAS NMR spectroscopy, it has been possible to study the mode of action of different allergens, from their possible activation through the metabolic pathway to the binding with epidermal proteins
Roland, Nathalie. "Interactions des fibres alimentaires avec les enzymes du métabolisme des xénobiotiques chez le rat : hétéroxenise avec une flore humaine". Paris 11, 1994. http://www.theses.fr/1994PA114830.
Texto completoCabaret, Odile. "Rôle des enzymes du métabolisme des xénobiotiques dans la toxicité pulmonaire de deux mycotoxines d’Aspergillus versicolor et d’Aspergillus nidulans". Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST0003.
Texto completoHuman health effects of inhaled mycotoxins remains poorly documented, despite these toxins are present in fungal spores et can directly reach the airway epithelia. Xenobiotic metabolozing enzymes can modulate lung toxicity of these mycotoxins through detoxification or reactive metabolite formation. Our aim was to study in vitro the metabolism and the cellular toxic consequences of two mycotoxins present in mold-contaminated environments, e.g. sterigmatocystin and methoxy-sterigmatocystin. The metabolism studies using recombinant cytochromes P450 enzymes and porcine tracheal epithelial cell primary cultures, showed that these mycotoxins could be oxidized by cytochrome P450 1A and conjugated by glucucoridation and sulfo-conjugation. Sterigmatocystin and methoxysterigmatocystin seem mainly detoxified in respiratory cells. If a metabolic activation of sterigmatocystin is possible, it seems limited
Jigorel, Émilie. "Transporteurs hépatiques de xénobiotiques : optimisation des modèles in vitro d’analyse et applications aux paramètres régulant leur expression et/ou activité". Rennes 1, 2006. http://www.theses.fr/2006REN1S088.
Texto completoBosquier, Hélène. "Maintien de fonctions hépatospécifiques du métabolisme des xénobiotiques dans une lignée hépatocytaire (mhPKT) issue d'une souris transgénique exprimant L-PK/TAg". Paris 5, 1997. http://www.theses.fr/1997PA05P003.
Texto completoChahin, Abir. "Bioindicateurs métaboliques de l'exposition des ruminants laitiers aux Hydrocarbures Aromatiques Polycycliques (HAP) : domaines scientifiques : biochimie, métabolisme des xénobiotiques, biologie animale". Thesis, Vandoeuvre-les-Nancy, INPL, 2010. http://www.theses.fr/2010INPL031N/document.
Texto completoPolycyclic aromatic hydrocarbons (PAH) are persistent organic pollutants (POP) produced during the incomplete burning of organic materials. Their production can be of natural origin (forest fire) or anthropic origin (gaz heating, vehicular traffic, industry). The ingestion of PAH contaminated vegetal covers or soils by farm animals, coupled with the high lipophily of these PAH, therefore represents a potential hazard in terms of contamination of animal products (milk, meat, eggs…). In the present work, we focused on the evaluation of the dairy ruminant exposure to PAH through the use of metabolic biomarkers of exposure. At first we tested the potential of 1-hydroxypyrene excreted in urine or milk to be used as a metabolic and specific biomarker of subchronic (7 to 40 days) and oral exposure of the goat to a ternary mixture consisting of phenanthrene, pyrene and benzo(a)pyrene. Each PAH was solubilized in oil to reach contamination levels in the range 0.04-50 mg/day. Results demonstrate that (i) 1-hydroxypyrene excretion in milk and urine is proportional to the level of exposure all along the tested exposure range (stable transfer rates of 1-OH pyrene: about 1% in milk and 10 % in urine); (ii) excretion of 1-OH pyrene reached a plateau at the latest 10 days after the beginning of exposure. In the second part of this work, it was demonstrated that the ethoxyresorufin-o-deethylase (EROD) activity, when measured in peripheral blood lymphocytes (PBL), can be used as a convenient and non-specific biomarker of oral and chronic exposure of dairy ruminant to CYP 450 inducting POP, such as many PAH. Induction kinetic of EROD activity PBL could be fitted with a logistic-like model over 40 days of exposure followed by 10 days post-exposure. An approximate dose/response curve could be fitted using a Michaelis-Menten-like model, allowing for several comments about the metabolism of PAH in dairy ruminant. A final kinetic study, which was run on rats under subchronic conditions (32 days), next to other results, showed a good correlation between EROD activities in PBL, liver and brain. Achieved results demonstrate the relevance of the combined use of the EROD activity in PBL and of the 1-OH pyrene in milk or urine as convenient and cost-limited tools for risk assessment in terms of PAH and more generally POP ingestion by dairy ruminants
Leininger-Muller, Brigitte. "La conjugaison des xenobiotiques dans le cerveau : localisation de l'activité de deux enzymes et étude in vivo de l'élimination d'un glucuronide". Nancy 1, 1992. http://www.theses.fr/1992NAN10419.
Texto completoLe, Fol Vincent. "Approche in vivo/in vitro du métabolisme de perturbateurs endocriniens chez le poisson zèbre (Danio rerio)". Phd thesis, Toulouse, INPT, 2015. http://oatao.univ-toulouse.fr/15125/1/lefol_1.pdf.
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