Aluminium Distribution and Excretion: A Comparative Study of a Number of Chelating Agents in Rats

The present study was conducted to assess in rats the comparative effects of a number of chelating agents on the urinary excretion and tissue distribution of A1. Adult male Sprague-Dawley rats received a single intraperitoneal dose of aluminium (A1) nitrate nonahydrate (0.24 mmol/kg). Ten min. after A1 injection 1,2-dimethyl-3-hydroxypyrid-4-one, 2,3-dihydroxybenzoic acid, picolinic acid, methylmalonic acid, ethylenediamine-di(o-hydroxyphenylacetic) acid, 1-benzyl-2-methyl-3-hydroxypyrid-4-one, 1-(p-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-methoxy-benzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-benzyl-2-ethyl-3-hydroxypyrid-4-one, 1-(p-methyl-benzyl)-2-ethyl-3-hydroxypyrid-4-one, 1-[3-hydroxy-2-methyl-4-oxopyridyl]-2-ethanesulfonic acid and 1-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-oxopyridine were given by gavage at 1.79 mmol/kg. A control group received similar volumes of distilled water. An additional group of rats received a subcutaneous injection of desferrioxamine at 1.79 mmol/ kg. Urine samples were collected daily for three consecutive days and the animals were killed after this period. Samples of brain, bone, liver, kidney and spleen were collected. Although desferrioxamine, 1,2-dimethyl-3-hydroxypirid-4-one, 1-(p-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-methoxybenzyl)-2-methyl-3- hydroxypyrid-4-one, 1-(p-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one, 1-[3-hydroxy-2-methyl-4-oxopyridyl]-2-ethanesulfonic acid and 1-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-osopyridine significantly enhanced the total excretion of A1 into urine, only treatment with 1-(p-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one and 1-benzyl-2-ethyl-3-hydroxypyrid-4-one significantly reduced A1 concentrations in all analyzed tissues. No beneficial effects of the remaining chelators on Al mobilization were observed. Further studies on the effects of some 3-hydoxrypyrid-4-ones on A1 removal can be of interest for the treatment of A1 accumulation and toxicity.