螯合剂对铀在小鼠体内分布的影响研究

Influence of Chelating Agents on Bio-distribution of Uranium in Mice

  • 摘要: 铀在生物体内的化学形态及分布是评价铀毒性的基础。文章通过尾静脉注射给药方式研究螯合剂对染铀小鼠体内铀分布的影响。通过建立包含主要体液金属离子、小分子配体及UO22+与螯合剂的热力学平衡模型,采用数值模拟方法研究UO22+在血液中的形态。实验结果表明:DTPA易与UO22+形成(UO2)2(OH)DTPA2-,对小鼠血液中的UO22+有明显的促排作用,但在促排的同时对小鼠的肾脏和骨骼有损伤;抗坏血酸对小鼠体内各组织器官的铀促排几乎无作用,但形成的(UO2)2(OH)Ascorbate2+会阻碍肾脏中U(Ⅵ)的代谢;NTA对小鼠体内各组织器官铀的促排作用小,并会促使体内出现固相(UO2)3(PO4)2·4H2O,对骨骼有较强的损伤作用,不适合作为铀的促排剂。

     

    Abstract: Tissue distribution of UO22+ in mice was investigated with dose of 5 mgU/kg and different chelating agents. A thermodynamic equilibrium model, involved in major metal-ions, low molecular weight molecule ligands and chelating agents, was made to analyze the speciation of UO22+ in human fluid. Computer simulation indicates that UO22+ will easily exist as (UO2)2(OH)DTPA2- species when the presence of DTPA and UO22+ in the blood of mice can be significantly removed out, but to some extent will damage kidneys and bones at same time. In contrast, ascorbic acid prevents ordinary metabolism of uranium in kidneys of mice, without any effect on removal of uranium, unfortunately, the complex compound of UO22+ ion with ascorbic acid is (UO2)2(OH)Ascorbate2+ which will affect UO22+ normal removal from kidneys. It can be concluded that NTA has a little effect on removal of uranium in tissues and organs of mice and promote the UO22+ and PO43- ion from solid phase as (UO2)3(PO4)2·4H2O which will deposit on the bone surface.

     

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