1.The toxicological mechanisms and detoxification of depleted uranium exposure.
Yong-Chao YUE ; Ming-Hua LI ; Hai-Bo WANG ; Bang-Le ZHANG ; Wei HE
Environmental Health and Preventive Medicine 2018;23(1):18-18
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.
Animals
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Chelating Agents
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pharmacology
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Humans
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Inactivation, Metabolic
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Radiation-Protective Agents
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pharmacology
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Uranium
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metabolism
;
toxicity
2.Uranyl Nitrate Induced Polyuric Acute Tubular Necrosis in Rats.
In Kyoung LIM ; Kee Ho LEE ; Byung Don HAN ; Ja Jun JANG ; Taik Koo YUN
Yonsei Medical Journal 1987;28(1):38-48
We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.
Animal
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Kidney Failure, Acute/chemically induced*
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Kidney Function Tests
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Kidney Tubular Necrosis, Acute/chemically induced*
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Male
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Rats
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Rats, Inbred Strains
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Uranium/pharmacology*
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Uranyl Nitrate/pharmacology*
3.Detoxication effect of water-soluble imprinted cross-linked chitosan on depleted uranium induced toxicity to renal cells.
Xiao-fei ZHANG ; Chao LI ; Chang-qi ZHAO ; Li-hong LIU
Acta Pharmaceutica Sinica 2011;46(5):513-520
To investigate whether a series of water-soluble cross-linked chitosan derivates synthesized in the guide of imprinting technology could be used as a uranium chelating agent to protect cells exposed to depleted uranium (DU), the imprinted chitosan derivates with high UO2(2+) chelating ability were screened, and cell model of human renal proximal tubule epithelium cells (HK-2) exposed to DU (500 micromol.L-1) was built, chitosan derivates (400 mg.L-1 ) was added to test group and diethylenetriaminepentaacetic acid (DTPA, 50 mg.L-1) was added to positive control group. The results showed that three Cu2+ imprinted chitosan derivates had higher uranium chelating ability (>49 microg.mg-1) than chitosan and non-imprinted chitosan derivates. Compared to the cells exposed to DU only, survival of cells in group added chitosan derivates rose up significantly (increased from 57.3% to 88.7%, and DTPA to 72.6%), and DU intracellular accumulation decreased, membrane damage and DNA damage also eased. Among the imprinted chitosan derivates, Cu2+ imprinted penta dialdehyde cross-linked carboxymethyl chitosan (Cu-P-CMC) was the best, and better than DTPA. From ultrastructure observation, the DU precipitates of test group added Cu-P-CMC were most grouped in a big hairy clusters in a string together outside cells. It is possible that the DU-chitosan derivates precipitates are too big to enter into cells, and from this way, the DU uptake by cells decreased so as to detoxication.
Antioxidants
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metabolism
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Apoptosis
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drug effects
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Cell Line
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Cell Survival
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drug effects
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Chelating Agents
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administration & dosage
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chemistry
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pharmacology
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Chitosan
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administration & dosage
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analogs & derivatives
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chemistry
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pharmacology
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Copper
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chemistry
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pharmacology
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Cross-Linking Reagents
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administration & dosage
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chemistry
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pharmacology
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DNA Damage
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drug effects
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Epithelial Cells
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cytology
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ultrastructure
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Humans
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Inactivation, Metabolic
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Kidney Tubules, Proximal
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cytology
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ultrastructure
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Microscopy, Electron, Transmission
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Uranium
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toxicity
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Water
4.Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro.
Yi-zhong BAO ; Dan WANG ; Yu-xing HU ; Ai-hong XU ; Mei-zhen SUN ; Hong-hong CHEN
Acta Pharmaceutica Sinica 2011;46(11):1308-1313
This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.
Animals
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Cell Line
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Cell Survival
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drug effects
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Chelating Agents
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administration & dosage
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chemistry
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pharmacology
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Dose-Response Relationship, Drug
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Epithelial Cells
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cytology
;
metabolism
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Humans
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Kidney
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metabolism
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Kidney Tubules, Proximal
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cytology
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Male
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Micronucleus Tests
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Molecular Structure
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Organometallic Compounds
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toxicity
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species
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metabolism
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Uranium
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metabolism
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urine