Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

Introduction: Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake.

Objectives: In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L; duration: 9 months, n = 10).

Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown.

Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.

The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties.

Uranium modifies or not behavior and antioxidant status in the hippocampus of rats exposed since birth.

In view of the known sensitivity of the developing central nervous system to pollutants, we sought to assess the effects of exposure to uranium (U) - a heavy metal naturally present in the environment - on the behavior of young rats and the impact of oxidative stress on their hippocampus. Pups drank U (in the form of uranyl nitrate) at doses of 10 or 40 mg.L(-1) for 10 weeks from birth.

Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity.

Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects.

Unexpected lack of deleterious effects of uranium on physiological systems following a chronic oral intake in adult rat.

Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.

Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions.

Molecular, cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes.

Enzymes that metabolize xenobiotics (XME) are well recognized in experimental models as representative indicators of organ detoxification functions and of exposure to toxicants. As several in vivo studies have shown, uranium can alter XME in the rat liver or kidneys after either acute or chronic exposure. To determine how length or level of exposure affects these changes in XME, we continued our investigation of chronic rat exposure to depleted uranium (DU, uranyl nitrate).

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.

Influence of environmental enrichment and depleted uranium on behaviour, cholesterol and acetylcholine in apolipoprotein E-deficient mice.

Alzheimer's disease is associated with genetic risk factors, of which the apolipoprotein E (ApoE) is the most prevalent, and is affected by environmental factors that include education early in life and exposure to metals. The industrial and military use of depleted uranium (DU) resulted in an increase of its deposition in some areas and led to a possible environmental factor. The present study aims to ascertain the effects on the behaviour and the metabolism of cholesterol and acetylcholine of ApoE-/- mice exposed to enriched environment (EE) and exposed to DU (20 mg/L) for 14 weeks.

Intranasal exposure to uranium results in direct transfer to the brain along olfactory nerve bundles.

Aims: Uranium olfactory uptake after intranasal exposure raises some concerns for people potentially exposed to airborne radionuclide contamination as the brain could be a direct target for these contaminants. A model of nasal instillation was used to elucidate the transport mechanisms of uranium to the brain and to map its localization.

Methods: Increasing concentrations of depleted uranium containing solutions were instilled in the nasal cavity of adult male rats.

Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats.

Uranium nanoparticles (<100 nm) can be released into the atmosphere during industrial stages of the nuclear fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account.

Chronic exposure to natural uranium via drinking water affects bone in growing rats.

Background: Bone is the main site of uranium accumulation after long term contamination. Several studies describe that at high dose of exposure, uranium impairs bone growth. Nevertheless little is known about the effects of chronic exposure at low doses of this radionuclide on bone, especially when ingested via drinking water, which is considered as the main exposure pathway for the public.

Cholesterol 7alpha-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat.

Depleted uranium (DU) is a radioactive heavy metal derived from the nuclear energy production. Its wide use in civilian and military items increases the risk of its environmental dissemination, and thus the risk of internal contamination of populations living in such contaminated territories. Previous studies have shown that vitamin D and cerebral cholesterol metabolisms were affected following chronic ingestion of DU.

Role of the olfactory receptor neurons in the direct transport of inhaled uranium to the rat brain.

Uranium presents numerous industrial and military uses and one of the most important risks of contamination is dust inhalation. In contrast to the other modes of contamination, the inhaled uranium has been proposed to enter the brain not only by the common route of all modes of exposure, the blood pathway, but also by a specific inhalation exposure route, the olfactory pathway. To test whether the inhaled uranium enter the brain directly from the nasal cavity, male Sprague-Dawley rats were exposed to both inhaled and intraperitoneally injected uranium using the (236)U and (233)U, respectively, as tracers.

Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure.

Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.

Incorporation and distribution of uranium in rats after a contamination on intact or wounded skin.

Uranium uptake can occur accidentally by inhalation, ingestion, injection, or absorption through intact or wounded skin. Intact or wounded skin routes of absorption of uranium have received little attention. The aims of our work were (1) to evaluate the influence of the type of wound contamination on the short term distribution and excretion of uranium in rats and (2) to generate data to assess the time available to treat contamination of intact or wounded skin before significant uptake of uranium occurs.

Accumulation and distribution of uranium in rats after chronic exposure by ingestion.

Data describing the biokinetics of radionuclides after contamination come mainly from experimental acute exposures of laboratory animals and follow-up of incidental exposures of humans. These data were compiled to form reference models that could be used for dose calculation in humans. In case of protracted exposure, the same models are applied, assuming that they are not modified by the duration of exposure.

Renal toxicogenomic response to chronic uranyl nitrate insult in mice.

Although the nephrotoxicity of uranium has been established through numerous animal studies, relatively little is known about the effects of long-term environmental uranium exposure. Using a combination of conventional biochemical studies and serial analysis of gene expression (SAGE), we examined the renal responses to uranyl nitrate (UN) chronic exposure. Renal uranium levels were significantly increased 4 months after ingestion of uranium in drinking water.