Influence of hydroxypyridones and desferrioxamine on the mobilization of aluminium from tissues of aluminium-loaded rats.
Significantly increased levels of aluminium were assayed in the liver and various brain regions of male Wistar rats after intra-peritoneal injection of aluminium gluconate for a period of 1-2 months. Cessation of aluminium gluconate administration for one month did not alter the tissue content of aluminium, apart from the spleen and hippocampus, indicating temporal stability of the aluminium loading. Administration of desferrioxamine, or one of the hydroxypyridone chelators, decreased tissue aluminium content in the liver and in all regions of the brain investigated. Desferrioxamine was more effective in mobilizing liver aluminium than either of the two hydroxypyridones, CP20 and CP94, whereas the more hydrophobic of the hydroxypyridones, diethyl hydroxypyrid-4-ones, (CP94), was most effective in mobilizing brain aluminium. From the present study it appears that orally active chelators of appropriate hydrophobicity may be extremely effective in mobilizing brain aluminium.
Florence
A L
AL
Unité de Biochimie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Gauthier
A
A
Ward
R J
RJ
Crichton
R R
RR
D000535:Aluminum / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000502:physiology
D000931:Antidotes; D011728:Pyridones; D000535:Aluminum; D003676:Deferoxamine