Graff L, Muller G, Burnel D
Laboratoire de Chimie Générale Appliquée à la Médecine, Faculté de Médecine, Université Henri Poincaré, Nancy, France.
Res Commun Mol Pathol Pharmacol. 1995 Jun;88(3):271-92.
Since desferrioxamine exhibits toxic effects, the possible use of several other therapeutic agents in acute aluminum intoxication has been investigated in this study. The potential for the chelation of aluminum (Al) by different compounds has been first determined using two in vitro techniques. The formation of stable complexes with Al in an aqueous solution has been evaluated by using pulse polarography. This technique allows the influence of temperature and of calcium (Ca) to be studied for each compound. Certain compounds (HEDTA, DTPA) showed extensive chelation in the presence of Ca2+ at a temperature of 37 +/- 1 degree C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy (A.E.S.) has allowed the ability of different substances to complex Al that was previously bound to serum proteins, to be estimated. The kinetics of chelation and the minimum efficient concentration have been determined for all of the products studied. The real efficacies of the compounds were studied by in vivo investigations to compare the effectiveness of the best chelating agents (DFO, HEDTA and EDTA) on the distribution and excretion of Al, after repeated i.p. administration to rats. HEDTA shows a chelation potential as widely active as the DFO potential.
由于去铁胺具有毒性作用，本研究对几种其他治疗药物在急性铝中毒中的可能应用进行了研究。首先使用两种体外技术确定了不同化合物对铝（Al）的螯合潜力。通过脉冲极谱法评估了在水溶液中与Al形成稳定络合物的情况。该技术可以研究每种化合物的温度和钙（Ca）的影响。某些化合物（HEDTA、DTPA）在37±1℃的温度下，在Ca2+存在时表现出广泛的螯合作用。一种超滤技术与通过原子发射光谱法（A.E.S.）测定Al相结合，可以估计不同物质络合先前与血清蛋白结合的Al的能力。已经确定了所有研究产品的螯合动力学和最低有效浓度。通过体内研究比较了最佳螯合剂（去铁胺、HEDTA和EDTA）在对大鼠反复腹腔注射后对Al的分布和排泄的有效性，从而研究了这些化合物的实际疗效。HEDTA显示出与去铁胺潜力一样广泛的螯合潜力。
