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Removal of vanadium by combining desferrioxamine and deferiprone chelators in rats

机译:去铁胺和去铁酮螯合剂联合去除大鼠中的钒

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Investigations were conducted to evaluate the ability of two chelators, desferrioxamine (DFO), and deferiprone (1,2-dimethy1-3-hydroxypyride-4-one, L1), for the excretion of vanadium after a period of administration of vanadium salts in 6-week-old male Wistar rats. Immediately after 60 days of vanadium administration, the rats received chelators (L1, DFO or L1 + DFO) for a period of 1 week. Chelators were given orally (L1), intraperitoneally (DFO), or both to different groups of rats at two different dosage levels. After chelation therapy, animals were sacrificed by exsanguination from abdominal aorta. Blood, kidney, liver, and heart samples were collected and prepared for determination of vanadium and iron concentrations by graphite furnace and flame atomic absorption spectroscopy (GF AAS, and F AAS) methods, respectively. These chelators significantly enhanced the urinary and biliary excretion of vanadium and restored the altered levels of iron. Furthermore, the hypothesis that these two known chelators might be more effective in removing vanadium from the body as a combined treatment than as monotherapy also was tested in this study. Although there is no significant difference between these two chelators in reducing the vanadium concentration, combination therapy (L1 + DFO) may cause higher efficacy and lower toxicity compared with monotherapies. Collectively, the results indicate that the designed procedure might be useful for preliminary in vivo testing of the efficiency of a chelating agent. However, our findings regarding the efficacy of combination therapy should be confirmed in more experiments. This preliminary study does not provide all answers to the magnitude of the efficiency of chelating agents in vanadium toxicity, and thus, further research is warranted.
机译:进行了研究,以评估两种螯合剂,去铁胺(DFO)和去铁酮(1,2-二甲基1-3-羟基吡啶-4-酮,L 1 )清除钒后的排泄能力。在六周大的雄性Wistar大鼠中施用钒盐的时间。服用钒60天后,大鼠立即接受螯合剂(L 1 ,DFO或L 1 + DFO),为期1周。螯合剂分别以两种不同的剂量口服给予不同组的大鼠(L 1 ),腹膜内(DFO)或两种。螯合治疗后,通过放血从腹主动脉处死动物。收集血液,肾脏,肝脏和心脏样本,并分别通过石墨炉和火焰原子吸收光谱法(GF AAS和F AAS)制备钒和铁的浓度。这些螯合剂显着增强了钒的尿和胆汁排泄,并恢复了铁水平的改变。此外,在这项研究中还检验了以下假设:这两种已知的螯合剂作为联合疗法比单药疗法更能有效地从体内去除钒。尽管这两种螯合剂在降低钒浓度方面没有显着差异,但是与单一疗法相比,联合疗法(L 1 + DFO)可能会导致更高的疗效和更低的毒性。总体而言,结果表明,所设计的方法可能对体内螯合剂效率的初步测试有用。但是,我们有关联合治疗功效的发现应在更多实验中得到证实。这项初步研究并未就螯合剂对钒毒性的效力程度提供所有答案,因此,有必要进行进一步研究。

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    《Medicinal Chemistry Research 》 |2010年第8期| p.854-863| 共10页
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