P. Houpert

Bioaccumulation and behavioural effects of depleted uranium in rats exposed to repeated inhalations

Depleted uranium has numerous industrial and military uses. Contamination by inhalation of airborne compounds is probably the most important route of exposure. In humans, there are no data clearly demonstrating neurotoxicity of uranium, yet some experimental studies suggest a link between neurological toxicity and uranium exposure. In this work, the bioaccumulation of uranium in male rats after exposure to repeated depleted uranium dioxide inhalation (30 min inhalation at 197 mgm(-3), 4 days a week for 3 weeks) has been studied, together with the behavioural effects. The uranium concentrations in the brain 1 day after the end of the exposure period varied as follows: olfactory bulb>hippocampus>frontal cortex>cerebellum, subsequently decreasing rapidly. The spontaneous locomotion activity of exposed rats was increased 1 day post exposure and the spatial working memory was less efficient 6 days post exposure, compared with control rats. These data suggest that depleted uranium is able to enter the brain after exposure to repeated inhalation, producing behavioural changes.

Efficacy of ethane-1-hydroxy-1, 1-bisphosphonate (EHBP) for the decorporation of uranium after intramuscular contamination in rats

PURPOSE To obtain compounds that will effectively reduce the fixation of uranium in its main target organs: bone and kidney. There is an urgent need for a chelating agent that is suitable and available for human use. MATERIALS AND METHODS The efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP), already in use as a therapeutic agent, was investigated in animal experiments. The effect of different treatment regimens was investigated on rats (EHBP: 50-100 micromol kg(-1); ligand/uranium ratio 2500 to 5000). RESULTS The present study shows that one prompt injection of EHBP reduced uranium deposition in kidneys by a factor of five after acute intramuscular contamination in rats. At the same time, the total body uranium in the treated animals was 70% of controls. When the treatment was delayed 30 min after contamination, the kidney content was still reduced by a factor of two. CONCLUSIONS EHBP has the advantage of clinical acceptance as a therapeutic agent for other purposes and its toxicity has been well studied. It therefore has a role in the treatment of human contamination with uranium.

Comparison of the effects of enriched uranium and 137-cesium on the behaviour of rats after chronic exposure

Purpose: A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure – uranium and cesium. Materials and methods: Rats were exposed for 9 months to drinking water contaminated with either enriched uranium at a dosage of 40 mg U · l−1 or 137-cesium at a dosage of 6500 Bq · l−1, which correspond to the highest concentrations measured in some wells in the south of Finland (uranium) or in the milk in Belarus in the year following the Chernobyl accident (137-cesium). Results: At this level of exposure, 137-cesium had no effect on the locomotor activity measured in an open-field, on immobility time in a forced swimming test, on spontaneous alternation in a Y-maze and on novel object exploration in an object recognition test. Enriched uranium exposure specifically reduced the spontaneous alternation measured in the Y-maze after 3 and 9 months exposure although it did not affect the other parameters. Conclusion: Enriched uranium exposure altered the spatial working memory capacities and this effect was correlated with previously described accumulation of uranium in the hippocampus which is one of the cerebral areas involved in this memory system.

The effects of the initial lung deposit on uranium biokinetics after administration as UF4 and UO4

This study was designed to assess the effect of the initial lung deposit (ILD) on uranium biokinetics in rats after intracheal instillation of biologically soluble uranium compounds. Rats received various doses of either UO4 or UF4 dust. The uranium content was determined in the kidneys, lungs, remaining carcass, urine and faeces at intervals of up to 30 days. The percentages of uranium absorbed into blood, transferred to tissues, and excreted in urine were independent of the uranium lung deposit for the two compounds. The K/K + U ratio 24 h after installation (K is the per cent of uranium retained in the kidneys and U the per cent excreted in urine) which can be used to evaluate kidney function, was essentially constant in the range from 0.02 to 12.5 microg U g(-1) kidneys.

Efficacy of 3,4,3-LIHOPO for reducing neptunium retention in the rat after simulated wound contamination

Purpose: The ligand 3,4,3-Li(1,2-HOPO) was tested for Np removal after intramuscular injection of 237 Np nitrate in rats. Materials and methods: Two experiments were performed, one with simultaneous injection of neptunium and LIHOPO at dosages ranging from 3 to 200mumolkg -1 and the other with delayed administration of LIHOPO 30mumolkg -1 from 5min to 30min after Np injection. Results: The data obtained after simultaneous injections showed that the ligand dosage effectiveness was not linear and depended on the tissues being considered. For bones, the best results were obtained with 200 mumolkg -1 LIHOPO, where retention was reduced to 11% of controls. Maximum efficacies for removal in liver and kidney were obtained with 30mumol kg -1 LIHOPO, where retention was reduced to 39% and 1.6% of controls, respectively. At higher dosages, LIHOPO seemed to have a reverse effect on these tissues, demonstrated by a significant accumulation of the radionuclide. The delayed administration of LIHOPO dramatically decreased its efficacy. When administered 5min after Np, LIHOPO was still efficient (60%, 37%, 7% of controls in bone, liver, kidneys, respectively) but not when treatment was delayed to 30min. Conclusions: These results demonstrated that LIHOPO was able to complex Np at the wound site but not after translocation to blood.PURPOSE The ligand 3,4,3-Li(1,2-HOPO) was tested for Np removal after intramuscular injection of 237Np nitrate in rats. MATERIALS AND METHODS Two experiments were performed, one with simultaneous injection of neptunium and LIHOPO at dosages ranging from 3 to 200 micromol kg(-1) and the other with delayed administration of LIHOPO 30 micromol kg(-1) from 5 min to 30 min after Np injection. RESULTS The data obtained after simultaneous injections showed that the ligand dosage effectiveness was not linear and depended on the tissues being considered. For bones, the best results were obtained with 200 micromol kg(-1) LIHOPO, where retention was reduced to 11% of controls. Maximum efficacies for removal in liver and kidney were obtained with 30 micromol kg(-1) LIHOPO, where retention was reduced to 39% and 1.6% of controls, respectively. At higher dosages, LIHOPO seemed to have a reverse effect on these tissues, demonstrated by a significant accumulation of the radionuclide. The delayed administration of LIHOPO dramatically decreased its efficacy. When administered 5 min after Np, LIHOPO was still efficient (60%, 37%, 7% of controls in bone, liver, kidneys, respectively) but not when treatment was delayed to 30 min. CONCLUSIONS These results demonstrated that LIHOPO was able to complex Np at the wound site but not after translocation to blood.