Health Effects of Naturally Radioactive Water Ingestion: The Need for Enhanced Studies

Background: Radiological pollution is a potentially important aspect of water quality. However, relatively few studies have been conducted to document its possible health effects

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

The neurotoxicology of uranium

International audienceThe brain is a target of environmental toxic pollutants that impair cerebral functions. Uranium is present in the environment as a result of natural deposits and release by human applications. The first part of this review describes the passage of uranium into the brain, and its effects on neurological functions and cognitive abilities. Very few human studies have looked at its cognitive effects. Experimental studies show that after exposure, uranium can reach the brain and lead to neurobehavioral impairments, including increased locomotor activity, perturbation of the sleep-wake cycle, decreased memory, and increased anxiety. The mechanisms underlying these neurobehavioral disturbances are not clearly understood. It is evident that there must be more than one toxic mechanism and that it might include different targets in the brain. In the second part, we therefore review the principal mechanisms that have been investigated in experimental models imbalance of the anti/pro-oxidant system and neurochemical and neurophysiological pathways. Uranium effects are clearly specific according to brain area, dose, and time. Nonetheless, this review demonstrates the paucity of data about its effects on developmental processes and the need for more attention to the consequences of exposure during development

Brain accumulation of inhaled uranium in the rat depends on aerosol concentration, exposure repetitions, particle size and solubility

International audienceA rostro-caudal gradient of uranium (U) in the brain has been suggested after its inhalation. To study thefactors influencing this mapping, we first used 30-min acute inhalation at 56 mg/m3 of the relatively soluble form UO4 in the rat. These exposure parameterswere then used as a reference in comparison with the other experimental conditions. Other groups received acute inhalation at different concentrations, repeated low dose inhalation of UO4 (10 exposures) or acute low dose inhalation of the insoluble form UO2. At 24 hafter the last exposure, all rats showed a brain U accumulation with a rostro-caudal gradient as compared to controls. However, the total concentration to the brain was greater after repeated exposure than acute exposure, demonstrating an accumulative effect. In comparison with the low dose soluble U exposure, a higher accumulation in the front of the brain was observed after exposure to higher dose, to insoluble particles and following repetition of exposures, thus demonstrating a dose effect and influences of solubility and repetition of exposures. In the last part, exposure to ultrafine U particles made it possible to show 24 h after exposure the presence of U in the brain according to a rostro-caudal gradient. Finally, the time-course after exposure to micronic or nanometric U particles has revealed greater residence times for nanoparticles

Memory and cholinergic system impaired by sub-chronic exposure to uranium in young rats

International audienc

Cerebral cortex and hippocampus respond differently after post-natal exposure to uranium

The central nervous system (CNS) is known to be sensitive to pollutants during its development. Uranium (U) is a heavy metal that occurs naturally in the environment as a component of the earth's crust, and populations may therefore be chronically exposed to U through drinking water and food. Previous studies have shown that the CNS is a target of U in rats exposed in adulthood. We assessed the effects of U on behavior and cholinergic system of rats exposed from birth for 10 weeks at 10 mg.L-1 or 40 mg.L-1. For behavioral analysis, the sleep/wake cycle (recorded by telemetry), the object recognition memory and the spatial working memory (Y-maze) were evaluated. Acetylcholine (ACh) and acetylcholinesterase (AChE) levels were evaluated in the entorhinal cortex and hippocampus. At 40 mg.L-1, U exposure impaired object recognition memory (-20%), but neither spatial working memory nor the sleep/wake cycle was impaired. A significant decrease was observed in both the ACh concentration (-14%) and AChE activity (-14%) in the entorhinal cortex, but not in the hippocampus. Any significant effect on behaviour and cholinergic system was observed at 10 mg U.L-1. These results demonstrate that early exposure to U during postnatal life induces a structure cerebral-dependant cholinergic response and modifies such memory process in rats. This exposure to U early in life could have potential delayed effects in adulthood