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Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
Subject(s)
Animals , Humans , Chelating Agents , Pharmacology , Inactivation, Metabolic , Radiation-Protective Agents , Pharmacology , Uranium , Metabolism , ToxicityABSTRACT
Objective To investigate the effects of glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling on the human renal proximal tubular epithelial HK-2 cell injury induced by depleted uranium(DU),and provide a new enlightenment for the development of DU antidotes.Methods H K-2 cells were exposed to different concentrations of DU for 3-24 h,then the protein expressions of kidney injury molecule 1 (KIM-1),neutrophil gelatinase-associated lipocalin (NGAL) and nuclear β-catenin were detected by immunofluorescence staining.The protein expressions of p-GSK-3 β(S9),GSK-3β and cmyc were detected by Western blot assay.HK-2 cells were transiently transfected by GSK-3β (KD) plasmid or treated by TDZD-8 to inhibit the activity of GSK-3β specifically.Other HK-2 cells were transiently transfected by β-catenin plasmid to overexpress the β-catenin protein.Results The percentages of KIM-1 and NGAL-positive cells increased with DU exposure time and concentrations from 300 and 600 μmol/L,and they were significantly higher than those of the blank control at 6-24 h of DU exposure (KIM-1-positive cells:t =11.06,18.97,30.49,P ＜0.05;t =6.79,16.02,85.45,P ＜ 0.05;NGAL-positive cells:t =11.78,11.37,34.29,P ＜0.05;t =7.34,21.63,36.84,P ＜0.05).In contrast,the ratio of p-GSK-3β (S9) to GSK-3β and percentage of nuclear β-catenin-positive cells were significantly higher than that of the blank control at 3-24 h of DU exposure (p-GSK-3β(S9)/GSK-3β:t =3.95,4.69,5.40,3.34,P ＜ 0.05;nuclear β-catenin-positive cells:t =4.61,6.52,36.64,14.93,P ＜ 0.05) with a maximum response at 9 h of DU exposure accompanied with corresponding increase of protein level of c-myc,a downstream target gene of β-catenin.Transient transfection of HK-2 cells with GSK-3β (KD) plasmid significantly inhibited the activity of GSK-3β (t =8.07,P ＜ 0.05) and reduced the DU-increased percentage of KIM-1-positive cells (t =24.77,P ＜ 0.05).Treatment cells with TDZD-8 inhibited the activity of GSK-3β and enhanced the percentage of nuclear β-catenin-positive cells,and it also significantly reduced the percentage of KIM-1-positive cells in HK-2 cells exposed to DU (t =6.25,6.73,P ＜ 0.05).Moreover,overexpression of β-catenin significantly reduced DU-induced cell injury (t =7.48,P ＜ 0.05).Conclusions GSK-3β/β-catenin signaling plays a key role in regulating the DU-induced cytotoxicity of HK-2 cells.Inhibition of GSK-3β activity and overexpression of β-catenin can protect the HK-2 cells from DU-induced damage.
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Objective To evaluate the impact of ghrelin on depleted uranium ( DU)-induced damage of the osteoblast MC3T3-E1. Methods MC3T3-E1 cells were treated with different doses of ghrelin for 1 h before DU (500 μM) treatment. After 24 hours,the cell via-bility,intracellular tartrate-resistant acid phosphatase (StrACP),alkaline phosphatase (AKP),osteoprotegerin (OPG),solvable receptor acti-vator of nuclear factor-κB ligand ( sRANKL) ,catalase ( CAT) and reactive oxygen species ( ROS) were measured. Results After DU expo-sure,ghrelin pretreatment increased the cell viability and CAT levels,and reduced intracellular StrACP,AKP,sRANKL/OPG and ROS in a dose-dependent manner. Conclusion Through maintaining the balance of OPG/RANKL and reducing the oxidative stress,ghrelin could pro-tect against DU-induced damage of MC3T3-E1 cells.
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Objective To explore the feasibility of using portable γ spectrometer to rapidly identify the low activity of depleted uranium and the underlying conditions.Methods Firstly,high purity germanium (Ge) γ spectrometer was used to analyze energy spectrum of DU samples (5 g) and calculate nuclide percentage of 235U in an attempt to ascertain the properties of these DU samples.The portable γ spectrometer was used to provide the evidences for identification of DU samples.Secondly,portable γ spectrometer was also used to identify DU samples of same group.These samples contain 1 g DU powder and 0-5 g environmental clay powder,which were sealed with double layer pocket,and then detected with a distance of 1-5 cm during the longest detection time of 10 min.According to the detection of nuclide activity of 238U and 235U in the samples and the subsequent calculation of specific activity,the nuclide percentage composition was calculated and the existence of DU was confirmed if this value of 235U was less than 0.718％.Results The activity of 238U was detected using portable γ spectrometer under all test conditions,while the activity of 235U was detectable only under certain test conditions (MA ≥ 1 g,DN ≤ 1 cm).Under the condition that the 238U and 235U was both detected,the nuclide percentage of 235U was all less than 0.718％,which suggested that the DU was confirmed.Conclusions The energy spectrum of low activity of DU and the type of nuclide could rapidly be identified and evaluated by using portable γ spectrometer.This is same as the conclusions obtained with high purity Ge γ spectrometer,α spectrometer and ICP-MS.
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Objective To investigate the effect of citric acid and ambroxol on clearing insoluble particles of depleted uranium in rat lungs by establishing a tracheal perfusion model.Methods One hundred and fifty male Wistar rats were randomly divided into model exposure group, normal control group(NC group), depleted uranium exposure group(DU), citric acid treatment group( CA) , ambroxol treatment group( AM) and citric acid+ambroxol treatment group( CA+AM) . The rats were sacrificed on 7, 15 and 30 days.Uranium content in the lungs was detected by microwave digestion method, pathological changes in the lungs were observed, and inflammatory factors of lung homogenates were detected.Results Compared to DU control group, the intrapulmonary uranium deposit amount in experimental groups was significantly reduced on 7 and 15 days (P<0.05).HE stained lung tissue showed that the pathological changes in treatment groups were less significant than in DU control group.The level of IL-1α,IL-1β,and IL-2 was significantly lower than in DU control, but the level of MCP-1 and MIP-1 was observably higher.Conclusion Citric acid and ambroxol can evidently improve the clear-ance of lung uranium and reduce damnification of lung tissues.Drug treatment can reduce the level of pulmonary inflamma-tory cytokines alleviate the chronic inflammation in the lungs, and enhance the capacity of macrophage to recruitment.
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Objective To study the effect of humic acid (HA) and soil on dissolution performance of depleted uranium (DU).Methods Using the static dissolve-adsorption experiment and inductively coupled plasma-mass spectrometry(ICP-MS) to determine uranium concentration and 235U/238U isotope ratios of the samples at different time and study the dissolution of DU in water.Results The solubility of DU in water was reduced by 90％ by adding HA.Soil could increase the solubility of DU in water by nearly 25％,adding an appropriate amount of HA could play a supporting role on the dissolution of DU,in this experiment adding 5％ of HA was best.Conclusions Soil and HA could produce positive and negative impact on the solubility of DU in water,and the combined effect of the two relied on the complex absorption and complexation reactions of soil,HA and dissolved uranium ions.
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Objective To observe the oxidative damage in human bronchial epithelial cells(BEAS-2B) induced by depleted uranium(DU)and protection of DMSO.Methods The measurement of extracellular superoxide anions(O2-·)was based on the reduction of ferricytochrome C.Quantitative analysis of extracellular hydrogen peroxides(H2O2)was used by the horseradish peroxidase-dependent oxidation of phenol red.The determination of extracellular hydroxyl radicals(·OH)was based on discoloration of safranine T.Ethidium bromide and 2,7'-dichlorofluorescein,fluorescent products of the membrane-permeable dyes-hydroethineand 2,7'-dichloroflurescin diacetate were used to monitor the intracellular production of O2-·and H2O2 by fluorometric method.The enzyme activity of SOD and GSH were measured by chemiluminescence and spectrophotometric method,respectively.Results The ROS production,including H2O2,O2-·and·OH,increased remarkably which induced by DU in BEAs-2B cells.The enzyme activity of SOD and GSH was descended remarkedly.These changes could be effectively inhibited by 0.5% of DMSO.Conclusions DU causes oxidative damage to BEAS-2B cells.Through removing active oxygen,DMSO can inhibit oxidative damage of DU.
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Objective To investigate the distribution of uranium in rats after inhalation with depleted uranium aerosols. Methods The depleted uranium aerosols were inhaled by Wistar rats. At 30, 90, 180, 270, 360, and 540 d after inhalation, the rata were sacrificed and tissue samples were collected. The contents of uranium in lung, kidney, liver, heart, brain, thighbone, spleen and thymus were measured by laser time-dependent spectroscopy analysis. Resulits The uranium contents of lung increased in the high-dosc and low-dose groups [(499833.3 ± 14214.8) ng/g and (25 424.0 ± 6193.4)ng/g, respectively] after inhalation, and significantly differed from the control (28.8 ± 13.9)ng/g, (P < 0.05).At 30 d after inhalation, the contents of uranium in lung, kidney and thighbone were higher than those of control, and then decreased time-dependently. At 60 d, the contents of uranium in liver, heart, brain, spleen and thymus were higher than those of control. Curve of the eontenta were biphasie, whieh went up first, reached at peak value and then went down. The contents of uranium were high in lung, thighbone, brain and thymus. Conclusions After inhalation of depleted uranium aerosols, lung and thighbone are the primary reservoirs for uranium redistributed, and accumulations in brain and thymus suggest other two organs for unanticipated injury by depleted uranium.
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Objective To explore the effect of long-term depleted uranium (DU)ingestion on testosterone production in rats, and its involvement mechanism. Methods Male and female rats (F0 and F1 respectively) for 160 days, respectively. The contents of testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum were detected in 20 months of F0 generations, and 15 months of F1 generations. RT-PCR was used to analyze the levels of StAR mRNA and P450scc mRNA. Results Compared with the normal control group, the testosterone contents in exposed F0 and F1 generations increased, the lowest was 51.73 U/L, but those of LH and FSH decreased. The expression of StAR mRNA in the low-doze group of F1 generation (StAR/β-actin = 1.35) was up-regulated, down-regulated for other groups.compared with the normal control group (P450scc/β-actin = 0. 313), the expression of P450scc mRNA in the low- and high-dose groups of F0 generation were decreased (P450scc/β-actin = 0.21), and those in the low- and high-dose groups of F1generation were increased (P450scc/β-actin = 0.623) (P ≤ 0.01). Conclusion Long-term DU exposure inhibit the male reproduction by intervening the sexual hormone production through down-regulated the expression of StAR mRNA and P450scc roRNA.
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Objective To evaluate the biological effect of a kind of protective cover against inhalation of depleted uranium (DU) dust particles. Methods At 1 and 3 d after inhalation of DU dust particles, uranium concentrations in the blood, lung, bronchia, kidney, and liver of the rats in the protected group and non protected group were measured and the efficiency of protection was calculated. Results Uranium levels in all tissues and fluids of the rats in the protected group decreased significantly to 71.2%-96.1% as compared with those in non protected group. Conclusion The protective cover is effective to reduce the harm due to inhalation of DU dust particles.
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Objective To find out the best method for elimination of uranium contamination in rat tissues as low as possible by removal of shrapnel fragments. Methods Experimental rats were divided into six groups: route group, decontamination before surgery group, decontamination in incision group, changing surgical appliances group, removing tissues around group, and comprehensive method group. Uranium concentrations in tissues and fluids in all groups were measured at 7, 14, and 21 d after operation. The efficiency of decontamination by different methods was compared. Results The highest uranium concentration in tissues was found in the route group, but the lowest in the comprehensive method group, and the second lowest in removing tissues around group. Conclusion The comprehensive method is the best one in all of the surgical removal methods. The soft tissues around DU shrapnels should be removed if they are not critical organs.
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Objective: To explore the protection of taurine-zinic coordination compound(TZC) against the neurotoxicity of depleted uranium (DU). Method: Rats were exposed to DU by different dosages intratracheal instillation of DU particles. One group was supplemented with TZC. Learning times in Y-labyrinth experiment, number of somatostatin positive cortical neurons were compared. Results: Learning times in Y-labyrinth experiment were increased in DU groups, and DU 5mg+TZC group was less than that of DU 5 mg group (P