Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

L’Uranium (U) est un métal lourd radioactif dispersé dans l’environnement. Du fait de cette présence naturelle mais aussi de ses applications civiles et militaires, la population générale peut être exposée à l’U par ingestion d’eau de boisson ou d’aliments contaminés. Le système pro/anti-oxydant est un système de défense fréquemment impliqué lors d'une exposition aiguë à l'uranium. L’objectif de cette thèse est d’étudier le rôle du système pro/anti-oxydant après contamination chronique à l’U dans le foie et les reins. Après contamination chronique de rats à différentes concentrations d’U, une accumulation dose dépendante de l’U dans les organes -jusqu'à 6 µg/g dans les reins- ainsi qu’une localisation préférentielle de l’U dans le noyau des cellules du tube contourné proximal sont observées. L’absence de néphrotoxicité observée, même à la plus forte concentration, pourrait s’expliquer par le renforcement du système anti-oxydant et notamment l’augmentation du taux de glutathion. L’étude des effets de la contamination à l’U chez un modèle déficient pour Nrf2, facteur de transcription cytoprotecteur impliqué dans la défense anti-oxydante, a mis en évidence une accumulation d’U plus importante chez les animaux Nrf2 -/-. Néanmoins, les effets biologiques de l’U sur le système pro/anti-oxydant ne semblent pas impliquer Nrf2. Par ailleurs, il existe une corrélation entre la localisation de l’U dans des cellules HepG2 en culture et les effets biologiques sur ce système après exposition à de faibles concentrations d’U. Ce radionucléide se localise dans les noyaux sous forme soluble et l’apparition de précipités est corrélée à la mise en place de mécanismes d’adaptation qui sont ensuite débordés au cours du temps et de la concentration, laissant apparaître une toxicité cellulaire. L’ensemble de ces résultats suggèrent que le renforcement du système anti-oxydant serait un mécanisme d’adaptation après exposition chronique à faible concentration d’U.Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 µg.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 -/- mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration

Statut antioxydant, au niveau rénal, après exposition chronique à l'uranium appauvri chez le rat

PARIS-BIUP (751062107) / SudocSudocFranceF

Rôle du stress oxydant au niveau hépatique et rénal dans la toxicité de l’uranium après exposition chronique

Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 µg.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 -/- mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration.L’Uranium (U) est un métal lourd radioactif dispersé dans l’environnement. Du fait de cette présence naturelle mais aussi de ses applications civiles et militaires, la population générale peut être exposée à l’U par ingestion d’eau de boisson ou d’aliments contaminés. Le système pro/anti-oxydant est un système de défense fréquemment impliqué lors d'une exposition aiguë à l'uranium. L’objectif de cette thèse est d’étudier le rôle du système pro/anti-oxydant après contamination chronique à l’U dans le foie et les reins. Après contamination chronique de rats à différentes concentrations d’U, une accumulation dose dépendante de l’U dans les organes -jusqu'à 6 µg/g dans les reins- ainsi qu’une localisation préférentielle de l’U dans le noyau des cellules du tube contourné proximal sont observées. L’absence de néphrotoxicité observée, même à la plus forte concentration, pourrait s’expliquer par le renforcement du système anti-oxydant et notamment l’augmentation du taux de glutathion. L’étude des effets de la contamination à l’U chez un modèle déficient pour Nrf2, facteur de transcription cytoprotecteur impliqué dans la défense anti-oxydante, a mis en évidence une accumulation d’U plus importante chez les animaux Nrf2 -/-. Néanmoins, les effets biologiques de l’U sur le système pro/anti-oxydant ne semblent pas impliquer Nrf2. Par ailleurs, il existe une corrélation entre la localisation de l’U dans des cellules HepG2 en culture et les effets biologiques sur ce système après exposition à de faibles concentrations d’U. Ce radionucléide se localise dans les noyaux sous forme soluble et l’apparition de précipités est corrélée à la mise en place de mécanismes d’adaptation qui sont ensuite débordés au cours du temps et de la concentration, laissant apparaître une toxicité cellulaire. L’ensemble de ces résultats suggèrent que le renforcement du système anti-oxydant serait un mécanisme d’adaptation après exposition chronique à faible concentration d’U

Rôle du stress oxydant au niveau hépatique et rénal dans la toxicité de l'uranium après exposition chronique

L Uranium (U) est un métal lourd radioactif dispersé dans l environnement. Du fait de cette présence naturelle mais aussi de ses applications civiles et militaires, la population générale peut être exposée à l U par ingestion d eau de boisson ou d aliments contaminés. Le système pro/anti-oxydant est un système de défense fréquemment impliqué lors d'une exposition aiguë à l'uranium. L objectif de cette thèse est d étudier le rôle du système pro/anti-oxydant après contamination chronique à l U dans le foie et les reins. Après contamination chronique de rats à différentes concentrations d U, une accumulation dose dépendante de l U dans les organes -jusqu'à 6 g/g dans les reins- ainsi qu une localisation préférentielle de l U dans le noyau des cellules du tube contourné proximal sont observées. L absence de néphrotoxicité observée, même à la plus forte concentration, pourrait s expliquer par le renforcement du système anti-oxydant et notamment l augmentation du taux de glutathion. L étude des effets de la contamination à l U chez un modèle déficient pour Nrf2, facteur de transcription cytoprotecteur impliqué dans la défense anti-oxydante, a mis en évidence une accumulation d U plus importante chez les animaux Nrf2 -/-. Néanmoins, les effets biologiques de l U sur le système pro/anti-oxydant ne semblent pas impliquer Nrf2. Par ailleurs, il existe une corrélation entre la localisation de l U dans des cellules HepG2 en culture et les effets biologiques sur ce système après exposition à de faibles concentrations d U. Ce radionucléide se localise dans les noyaux sous forme soluble et l apparition de précipités est corrélée à la mise en place de mécanismes d adaptation qui sont ensuite débordés au cours du temps et de la concentration, laissant apparaître une toxicité cellulaire. L ensemble de ces résultats suggèrent que le renforcement du système anti-oxydant serait un mécanisme d adaptation après exposition chronique à faible concentration d U.Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 g.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 -/- mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Elucidation of the decomposition pathways of protonated and deprotonated estrone ions: application to the identification of photolysis products.

International audienceWith the future aim of elucidating the unknown structures of estrogen degradation products, we characterized the dissociation pathways of protonated estrone (E1) under collisional activation in liquid chromatography/tandem mass spectrometry (LC/MS/MS) experiments employing a quadrupole time-of-flight mass spectrometer. Positive ion and negative ion modes give information on the protonated and deprotonated molecules and their product ions. The mass spectra of estrone methyl ether (CH(3)-E1) and estrone-d(4) (E1-d(4)) were compared with that of E1 in order (i) to elucidate the dissociation mechanisms of protonated and deprotonated molecules and (ii) to propose likely structures for each product ions. The positive ion acquisition mode yielded more fragmentation. The mass spectra of E1 were compared with those of estradiol (E2), estriol (E3) and 17-ethynylestradiol (EE2). This comparison allowed the identification of marker ions for each ring of the estrogenic structure. Accurate mass measurements have been carried out for all the identified ions. The resulting ions revealed to be useful for the characterization of structural modifications induced by photolysis on each ring of the estrone molecule. These results are very promising for the determination of new metabolites in the environment

Multiscale harmonised automated observations of phytoplankton biomass, diversity and productivity dynamics in the English Channel and North Sea as part of the coastal Pilot Super Site approach (JERICO S3)

International audienceMultiscale harmonised automated observation of phytoplankton is essential for accurately monitoring changes in marine coastal ecosystems state and functioning. Novel approaches are currently applied within the English Channel and North Sea coastal Pilot Super Site of the Joint European Research Infrastructure for Coastal Observatories (JERICO-S3) for provision of sustained multidisciplinary observations. This site is characterized by significant connectivity to adjacent seas, strong hydrodynamics and high riverine inputs, influencing biogeochemical and biological processes like high productivity and recurring phytoplankton blooms, some them of potential impact on marine food webs, as well as human health and economy. The intrinsic knowledge on phytoplankton biomass, diversity and productivity dynamics are completed, at different spatial and temporal scales, through the harmonisation of observations (including near-real time in vivo automated approaches implemented for almost a decade). Integrated phytoplankton observations are carried out combining reference methods with innovative automated in vivo imaging inflow/in situ/benchtop devices, automated flow cytometers, as well as multispectral/variable fluorometers, implemented in fixed autonomous stations, moorings, dedicated cruises and ships of opportunity (FerryBox). Functional and taxonomical diversity are addressed in the frame of different monitoring networks carried out in four contrasted ecosystems from the Celtic Seas and English Channel to the German Bight in the North Sea. Moreover, the models used to compute high resolution-resolved photosynthetic parameters and primary production using variable fluorescence measurements give insights into different seasonal patterns, which are respectively synchronous or in delay with that of chlorophyll biomass and community changes. These measurements provide a more precise information on the distribution and dynamics of phytoplankton functional groups (flow cytometry) and main taxa (imaging) at high spatial and temporal resolution assigning community changes to different bloom situations and pelagic habitats state, complementing physical, biogeochemical and biological variables. Finally, harmonisation in data pipelines conform to the FAIR principle and synthesis based on conventional statistics as well as on IA/ML approaches makes it possible to address scientific, societal and economic challenges through a new perspective, facing global and local changes

Multiscale harmonised automated observations of phytoplankton biomass, diversity and productivity dynamics in the English Channel and North Sea as part of the coastal Pilot Super Site approach (JERICO S3)

International audienceMultiscale harmonised automated observation of phytoplankton is essential for accurately monitoring changes in marine coastal ecosystems state and functioning. Novel approaches are currently applied within the English Channel and North Sea coastal Pilot Super Site of the Joint European Research Infrastructure for Coastal Observatories (JERICO-S3) for provision of sustained multidisciplinary observations. This site is characterized by significant connectivity to adjacent seas, strong hydrodynamics and high riverine inputs, influencing biogeochemical and biological processes like high productivity and recurring phytoplankton blooms, some them of potential impact on marine food webs, as well as human health and economy. The intrinsic knowledge on phytoplankton biomass, diversity and productivity dynamics are completed, at different spatial and temporal scales, through the harmonisation of observations (including near-real time in vivo automated approaches implemented for almost a decade). Integrated phytoplankton observations are carried out combining reference methods with innovative automated in vivo imaging inflow/in situ/benchtop devices, automated flow cytometers, as well as multispectral/variable fluorometers, implemented in fixed autonomous stations, moorings, dedicated cruises and ships of opportunity (FerryBox). Functional and taxonomical diversity are addressed in the frame of different monitoring networks carried out in four contrasted ecosystems from the Celtic Seas and English Channel to the German Bight in the North Sea. Moreover, the models used to compute high resolution-resolved photosynthetic parameters and primary production using variable fluorescence measurements give insights into different seasonal patterns, which are respectively synchronous or in delay with that of chlorophyll biomass and community changes. These measurements provide a more precise information on the distribution and dynamics of phytoplankton functional groups (flow cytometry) and main taxa (imaging) at high spatial and temporal resolution assigning community changes to different bloom situations and pelagic habitats state, complementing physical, biogeochemical and biological variables. Finally, harmonisation in data pipelines conform to the FAIR principle and synthesis based on conventional statistics as well as on IA/ML approaches makes it possible to address scientific, societal and economic challenges through a new perspective, facing global and local changes

Automated optical approaches for in vivo multiscale monitoring of phytoplankton communities and HABs in the English Channel and North Sea

International audienceAutomated optical observations of phytoplankton communities are currently implemented in eastern English Channel and southern North Sea on different platforms (fixed autonomous stations, moorings, dedicated cruises and measurements/ships of opportunity) as a complement of long term monitoring networks in the. These marginal seas are characterized by significant connectivity to adjacent ocean and seas, strong hydrodynamics and low to high riverine inputs, influencing biogeochemical and biological processes like high productivity and recurring phytoplankton blooms, including some Harmful Algal Blooms-HABs of potential impact on marine food webs, as well as on human health and economy. Integrated phytoplankton observations are carried out combining reference methods with innovative automated in vivo imaging inflow/in situ/benchtop devices, pulse shape-recording flow cytometers, as well as in vivo multispectral fluorometers. These measurements provide information on the distribution and dynamics of phytoplankton functional groups (flow cytometry) and main taxa (imaging) at high spatial and temporal resolution assigning community changes to different bloom situations and pelagic habitats state, complementing physical, biogeochemical and biological variables. The in vivo approaches allow tracking HABs at different spatial and temporal scales, through the harmonisation of observations (including near-real time in vivo automated approaches implemented for almost a decade), at almost real time, and become a helpful tool for managers of these events. Finally, harmonisation in data pipelines conform to the FAIR principle and synthesis based on conventional statistics as well as on IA/ML approaches makes it possible to address scientific, societal and economic challenges through a new perspective, facing global and local changes

Automated optical approaches for in vivo multiscale monitoring of phytoplankton communities and HABs in the English Channel and North Sea

International audienceAutomated optical observations of phytoplankton communities are currently implemented in eastern English Channel and southern North Sea on different platforms (fixed autonomous stations, moorings, dedicated cruises and measurements/ships of opportunity) as a complement of long term monitoring networks in the. These marginal seas are characterized by significant connectivity to adjacent ocean and seas, strong hydrodynamics and low to high riverine inputs, influencing biogeochemical and biological processes like high productivity and recurring phytoplankton blooms, including some Harmful Algal Blooms-HABs of potential impact on marine food webs, as well as on human health and economy. Integrated phytoplankton observations are carried out combining reference methods with innovative automated in vivo imaging inflow/in situ/benchtop devices, pulse shape-recording flow cytometers, as well as in vivo multispectral fluorometers. These measurements provide information on the distribution and dynamics of phytoplankton functional groups (flow cytometry) and main taxa (imaging) at high spatial and temporal resolution assigning community changes to different bloom situations and pelagic habitats state, complementing physical, biogeochemical and biological variables. The in vivo approaches allow tracking HABs at different spatial and temporal scales, through the harmonisation of observations (including near-real time in vivo automated approaches implemented for almost a decade), at almost real time, and become a helpful tool for managers of these events. Finally, harmonisation in data pipelines conform to the FAIR principle and synthesis based on conventional statistics as well as on IA/ML approaches makes it possible to address scientific, societal and economic challenges through a new perspective, facing global and local changes

Phytoplankton automated in vivo/in situ observations: towards a new approach of Essential Ocean Variables of marine coastal ecosystems.

International audienceAs phytoplankton is essential in supporting food webs and mediating biogeochemical cycles, it became crucial to complement discrete sampling and laboratory methods to address this compartment at its finest temporal and spatial scale. Within the “Joint European Research Infrastructure for Coastal Observatories – Novel EXperTise” (JERICO-NEXT), scientists proceeded to the exploration of novel phytoplankton automated in vivo/in situ techniques, based on single cell/particle or bulk optical characteristics. These techniques were implemented in a variety of monitoring platforms (fixed stations, moorings, research vessels, ships of opportunity), from oligotrophic (West Mediterranean) to mesotrophic and eutrophic marine coastal waters (English Channel, North Sea and Baltic Sea). These approaches could represent warning systems in water quality through phytoplankton total abundance and biomass, composition changes and the occurrence of blooms, including harmful algal blooms HAB, of special interest in areas of fishing, aquaculture and tourism. At the dawn of the UN Decade of the Ocean, the JERICO-S3 (Science, Services, Sustainability) project tends to generalise these approaches and seeks to standardise as much as possible their operability and capacity in addressing phytoplankton diversity and productivity, moving towards a new approach of Essential Ocean Variables (EOVs). Moreover, the development of automated tools for data analysis, using machine-learning and deep learning and will allow integrating these data into European marine data infrastructures available for research and marine management