Lote C J, Willmott K, Wood J A, Thewles A, Freeman M
Department of Physiology, University of Birmingham, UK.
Hum Exp Toxicol. 1995 Dec;14(12):945-8. doi: 10.1177/096032719501401202.
When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experiments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced aluminium excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excretion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excretion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sulphate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma aluminium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an aluminium load, to limit aluminium binding to ligands which allow it to enter cells.
给大鼠静脉注射铝时，铝的形态对其经肾排泄有重大影响。以柠檬酸盐形式给予的铝比以氯化物或硫酸盐形式给予的铝排泄得更有效。这表明柠檬酸盐对接触过铝的患者可能具有治疗作用。因此，我们在大鼠身上进行了两组实验，在静脉注射硫酸铝大剂量后，立即或一小时后开始静脉输注柠檬酸盐。与仅输注0.7%氯化钠的对照组相比，两种方案都导致铝排泄明显增加。如果在给予铝后立即开始输注柠檬酸盐，铝排泄增加783%；如果延迟一小时开始输注柠檬酸盐，铝排泄增加335%。排泄增加是由于铝的可自由滤过部分增加。在对照实验中，给予硫酸铝后输注0.7%氯化钠，发现铝沉积在肝脏中。在给予铝大剂量一小时后给予柠檬酸盐并不能减少肝脏中的这种沉积。结果表明，输注的柠檬酸盐能够作用于一部分血浆铝，从而将其转化为可滤过的形式并排出体外。似乎为了达到最大治疗效果，在铝负荷后应尽快输注柠檬酸盐，以限制铝与使其进入细胞的配体结合。
