ALUMINUM DISTRIBUTION AND EXCRETION - A COMPARATIVE-STUDY OF A NUMBEROF CHELATING-AGENTS IN RATS

The present study was conducted to assess in rats the comparative effe cts of a number of chelating agents on the urinary excretion and tissu e distribution of Al. Adult male Sprague-Dawley rats received a single intraperitoneal dose of aluminium (Al) nitrate nonahydrate (0.24 mmol /kg). Ten min. after Al injection, 1,2-dimethyl-3-hydroxypirid-4-one, 2,3-dihydroxybenzoic acid, picolinic acid, methylmalonic acid, ethylen ediamine-di(o-hydroxyphenylacetic) acid, 1-benzyl-2-methyl-3-hydroxypy rid-4-one, 1-(p-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, -(p-metho xy-benzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-chlorobenzyl)-2-methyl- 3-hydroxypyrid-4-one I-benzyl-2-ethyl-3-hydroxypyrid-4-one, 1-(p-methy lbenzyl)-2-ethyl-3-hydroxypyrid-4-one, [3-hydroxy-2-methyl-3-oxopyridy l]-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 g roup received similar volumes of distilled water. An additional group of rats received a subcutaneous injection of desferrioxamine at 1.79 m mol/ 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-hydrox ypyrid-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-oxopyridine significantly enhanced the total excre tion of Al into urine, only treatment with 1-(p-chlorobenzyl)-2-methyl -3-hydroxypyrid-4-one one and I-benzyl-2-ethyl-3-hydroxypyrid-4-one si gnificantly reduced Al concentrations in all analyzed tissues. No bene ficial effects of the remaining chelators on Al mobilization were obse rved. Further studies on the effects of some 3-hydoxrypyrid-4-ones on Al removal can be of interest for the treatment of Al accumulation and toxicity.