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F Paquet

Publications and source records attributed to F Paquet.

At least 19 recordsLinked to original sources
PubMed2006

Effect of acetaminophen administration to rats chronically exposed to depleted uranium.

The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40mg/l) were treated by acetaminophen (APAP, 400mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p<0.01) and AST (p<0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p<0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination.

Acetaminophen↗
PubMed2006

Parental exposure to enriched uranium induced delayed hyperactivity in rat offspring.

Several recent reports suggest that chronic exposure to uranium could induce behavioural effects in adult rats. As the immature brains are known to be more susceptible to toxic effects, rats were observed in an open field, in a Y-maze and in an elevated plus-maze at 2, 5 and 9 months old after exposure to enriched uranium (40 mg l-1) during gestation and lactation. The rats exposed to enriched uranium showed a significant decrease in alternation in the Y-maze at 2 months old which reflects a slight decrease in the spatial working memory capacities as previously described in adult rats. However, the main result was a delayed hyperactivity in the rats exposed to enriched uranium, which appeared to a slight extent at 5 months old and was more evident at 9 months old. Although this effect could not be directly explained by some uranium accumulation in the target organs, this experiment showed that early exposure to enriched uranium can induce a very late effect on the rat behaviour and that such studies should not be restricted to the effects observed on young rats.

Animals↗
PubMed2006

Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats.

Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of (137)Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with (137)Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3) metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders.

Animals↗
PubMed2006

Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat.

Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D(3) biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D(3)-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels.

Animals↗
PubMed2006

Short-term effects of depleted uranium on immune status in rat intestine.

In the event of ingestion, the digestive tract is the first biological system exposed to depleted uranium (DU) intake via the intestinal lumen. However, little research has addressed the biological consequences of a contamination with depleted uranium on intestinal properties such as the barrier function and/or the immune status of this tissue. The aim of this study was to determine if the ingestion of depleted uranium led to changes in the gut immune system of the intestine. The experiments were performed at 1 and 3 d following a per os administration of DU to rats at sublethal dose (204 mg/kg). Several parameters referring to the immune status, such as gene and protein expressions of cytokines and chemokines, and localization and density of immune cell populations, were assessed in the intestine. In addition, the overall toxicity of DU on the small intestine was estimated in this study, with histological appearance, proliferation rate, differentiation pattern, and apoptosis process. Firstly, the results of this study indicated that DU was not toxic for the intestine, as measured by the proliferation, differentiation, and apoptosis processes. Concerning the immune properties of the intestine, the ingestion of depleted uranium induced some changes in the production of chemokines and in the expression of cytokines. A diminished production of monocyte chemoattractant protein-1 (MCP-1) was noted at 1 day post exposure. At 3 d, the increased gene expression of interferon gamma (IFNgamma) was associated with an enhanced mRNA level of Fas ligand, suggesting an activation of the apoptosis pathway. However, no increased apoptotic cells were observed at 3 d in the contaminated animals. There were no changes in the localization and density of neutrophils, helper T lymphocytes, and cytotoxic T lymphocytes after DU administration. In conclusion, these results suggest that depleted uranium is not toxic for the intestine after acute exposure. Nevertheless, DU seems to modulate the expression and/or production of cytokines (IFNgamma) and chemokines (MCP-1) in the intestine. Further experiments need to be performed to determine if a chronic contamination at low dose leads in the long term to modifications of cytokines/chemokines patterns, and to subsequent changes in immune response of the intestine.

Animals↗
PubMed2006

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. This work aims at testing this hypothesis. It presents new experimental data on retention of uranium after chronic intake, which are compared to values calculated from a biokinetic model that is based on experiments of acute exposure of rats to uranium. Experiments were performed with 56 male Sprague Dawley rats, from which 35 were exposed during their whole adult life to 40 mg L of uranyl nitrate dissolved in mineral water and 21 were kept as controls. Animals were euthanatized at 32, 95, 186, 312, 368, and 570 d after the beginning of contamination. Urine and all tissues were removed, weighted, mineralized, and then analyzed for uranium content by Kinetics Phosphorescence Analysis (KPA) or by ICP-MS. Experimental data showed that uranium accumulated in most organs, following a nonmonotonous pattern. Peaks of activities were observed at 1-3, 10, and 19 mo after the beginning of exposure. Additionally, accumulation was shown to occur in tissues such as teeth and brain that are not usually described as target organs. Comparison with model prediction showed that the accumulation of uranium in target organs after chronic exposure is overestimated by the use of a model designed for acute exposure. These differences indicate that protracted exposure to uranium may induce changes in biokinetic parameters when compared to acute contamination and that calculation of dose resulting from chronic intake of radionuclides may need specific models that are not currently available.

Administration, Oral↗
PubMed2005

Chronic ingestion of uranyl nitrate perturbs acetylcholinesterase activity and monoamine metabolism in male rat brain.

Recent animal studies have shown that uranium can reach the brain after chronic exposure. However, little information is available on the neurological effects of chronic long-term exposure to uranium. In the present study, the effects during 1.5, 6 and 9-month periods of chronic ingestion of uranyl nitrate (UN) in drinking water (40 mg of uranium per litre) on cholinergic acetylcholinesterase (AChE) activity and on dopaminergic and serotoninergic metabolisms were investigated in several areas of male Srague Dawley rat brains. Uranium brain accumulation and distribution was also investigated after 1.5 and 9 months. Both after 1.5, 6 and 9 months of exposure, AChE activity was unaffected in the striatum, hippocampus and frontal cortex. Nevertheless, AChE activity was transitionally perturbed in the cerebellum after 6 months of exposure. After 1.5 months of exposure, DA level increased in hypothalamus. After 6 months of exposure, a tiny but significant modification of the DAergic turnover ratio was detected in the frontal cortex. And after 9 months, UN produced a significant decrease in the 5HIAA level and the 5HTergic turn-over ratio in the frontal cortex and also a decrease in the DOPAC level and DAergic turn-over ratio in the striatum. Uranium brain accumulation was statistically significant in striatum after 1.5 months and in striatum, hippocampus and frontal cortex after 9 months of exposure. Although neurochemical changes did not always correlated with increased accumulation of uranium in specific areas, these results suggest that chronic ingestion of UN can cause chronic and progressive perturbations of physiological level of neurotransmitter systems. Considering previous reports on behavioural uranium-induced effects and the involvement of neurotransmitters in various behavioural processes, it would be crucial to determine whether these neurochemical disorders were accompanied by neurobehavioral deficits even at 40 mg of uranium per litre exposure.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2005

The brain is a target organ after acute exposure to depleted uranium.

The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144+/-10 microg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 microg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70+/-8 microg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed.

Animals↗
PubMed2005

The chemical speciation of uranium in water does not influence its absorption from the gastrointestinal tract of rats.

Studies of the chemical speciation of uranium in water can enhance the knowledge of the mechanisms of its absorption from the gastrointestinal tract and its storage in the body. They can also help to improve the dosimetric models recommended by the International Commission on Radiological Protection (ICRP). The aim of this work was to assess the influence of uranium speciation on its absorption from the gastrointestinal tract by using both computer speciation modeling and direct measurement of the fractional absorption in vivo in rats after ingestion of five different samples of contaminated water. Preliminary ex vivo studies with human saliva and gastric juice showed that 90% of uranium was recovered with the natural components of the fluid studied. The computer studies of uranium speciation among the electrolytes of these fluids showed that under the set conditions, the chemical species changed in a broadly similar manner under the influence of fluid composition and pH. In vivo studies in rats validated these observations by indicating an average fractional absorption of about 0.4% for each of five different water samples. It is concluded that the chemical form of uranium in the water ingested did not influence its absorption into the body.

Animals↗
PubMed2005

Absorption of uranium through the entire gastrointestinal tract of the rat.

The aim was to determine the gastrointestinal segments preferentially implicated in the absorption of uranium. The apparent permeability to uranium (233U) was measured ex vivo in Ussing chambers to assess uranium passage in the various parts of the small and large intestines. The transepithelial electrical parameters (potential difference, short-circuit current, transepithelial resistance and tissue conductance) were also recorded for each segment. Determination of in vivo uranium absorption after in-situ deposition of 233U in digestive segments (buccal cavity, ileum and proximal colon) and measurements of uranium in peripheral blood were then made to validate the ex vivo results. In addition, autoradiography was performed to localize the presence of uranium in the digestive segments. The in vivo experiments indicated that uranium absorption from the digestive tract was restricted to the small intestine (with no absorption from the buccal cavity, stomach or large intestine). The apparent permeability to uranium measured with ex vivo techniques was similar in the various parts of small intestine. In addition, the experiments demonstrated the existence of a transcellular pathway for uranium in the small intestine. The study indicates that uranium absorption from the gastrointestinal tract takes place exclusively in the small intestine, probably via a transcellular pathway.

Animals↗
PubMed2004

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

Body Burden↗
PubMed2004

A local approach to reduce industrial uranium wound contamination in rats.

The aim of this work is to develop a new approach to partially decontaminate wounds after industrial uranium contamination, during the interval of time between contamination and transfer of the patient to the infirmary. A wound dressing and a paste mixed or not with uranium-chelating ligands, ethane-1-hydroxy-1,1-bisphosphonate (EHBP) and carballylic amido bis phosphonic acid (CAPBP), were tested in vitro on muscles and in vivo on rats after deposit of uranium oxide compounds. The dressing and the paste, composed of carboxymethylcellulose-based hydrocolloids known to be highly absorbent, were applied on simulated wounds a few minutes after the contamination. The incorporation of chelating ligands did not improve the efficacy of the dressing or paste, and the best results were obtained with the dressing. In vivo, after 1 h of contact with the wound, the dressing absorbed about 30% and 60% of a UO4 compound deposited intra- and intermuscularly, respectively. After intramuscular deposit, the efficacy of the dressing was not reduced if the contact time decreased from 1 h to 15 min. Therefore, this wound dressing could be a practical option to treat uranium-contaminated wounds, but its efficacy depends on the localization of the uranium deposit.

Administration, Cutaneous↗
PubMed2004

In vitro evaluation of percutaneous diffusion of uranyl nitrate through intact or excoriated skin of rat and pig.

At the present time, the International Commission on Radiological Protection (ICRP) has not published any model concerning internal radioactive contamination by uptake from wounds. The aims of our work were to determine the time available to treat contamination of intact or wounded skin before a significant uptake of uranium occurred and to evaluate the consequences of incomplete decontamination on uranium uptake. The kinetics of percutaneous diffusion of uranium through intact or excoriated skin and its distribution in skin layers were evaluated using an in vitro technique. Our data demonstrated a dramatic increase of uranium percutaneous diffusion through excoriated skin compared with intact skin. Significant uptake of uranium through excoriated skin occurred in only 30 min, indicating that there is only a short interval available to treat a contaminated wound effectively. Moreover, in the case of an incompletely decontaminated superficial wound, viable epidermis behaved as a reservoir for uranium that remained bioavailable. At the present time, potential uptake of uranium and perhaps other radionuclides through intact or wounded skin is not adequately taken into account by radiological protection agencies. Our results emphasize the need for further study and modeling of uptake of radionuclides through intact or wounded skin.

Administration, Cutaneous↗
PubMed2004

Effect of U and 137Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat.

Following the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by 137Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or 137Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U.L -1 or 6500 Bq 137Cs.L -1). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or 137Cs. These results are not in accordance with those previously described.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia.

The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D2) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine 123-IBZM (123I-IBZM), a radioligand with a high affinity and specificity for the D2 receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy. However, there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D2 receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.

Adult↗
PubMed2003

Characterisation and dissolution of depleted uranium aerosols produced during impacts of kinetic energy penetrators against a tank.

Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.

Aerosols↗
PubMed2003

The contribution of chemical speciation to internal dosimetry.

Speciation studies refer to the distribution of species in a particular sample or matrix. These studies are necessary to improve the description, understanding and prediction of trace element kinetics and toxicity. In the case of internal contamination with radionuclides, speciation studies could help to improve both the biokinetic and dosimetric models for radionuclides. There are different methods to approach the speciation of radionuclides in a biological system, depending on the degree of accuracy needed and the level of uncertainties accepted. Among them, computer modelling and experimental determination are complementary approaches. This paper describes what is known about speciation of actinides in blood, GI tract, liver and skeleton and of their consequences in terms of internal dosimetry. The conclusion is that such studies provide very valuable data and should be targeted in the future on some specific tissues and biomolecules.

Actinoid Series Elements↗