Effects of age and chelation therapy on tissue concentrations of essential elements in aluminum-loaded rats

Objective: To determine tissue concentrations of six essential elements (Ca, Cu, Fe, Mg, Mn and Zn) following chelation therapy in young and old aluminum- (Al) loaded rats. Methods: Young (21 days) and old (18 months) rats were given Al nitrate nonahydrate in drinking water at 50 mg Al/kg/day for 2 weeks. After this period, Al doses were increased to 100 mg/kg/day and administered for 100 days. Three groups of Al-loaded rats were given solutions of 1-(p-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one (MeBzEM) (oral), deferiprone (oral) and DFO (s.c.) for 5 days at doses of 0.89 mmol/kg. A fourth group of Al-loaded rats received a combined administration of deferiprone (oral) and DFO (s.c.) at 0.35 mmol/kg/day during 5 days. Two additional groups (young and old rats) received a s.c. injection of 0.9% saline and deionized water by gavage (positive control groups). Results: In the positive control groups. no age-related differences were noted in tissue Ca concentrations, while Fe was the most affected element. Iron levels in spleen, liver and kidney were significantly higher in old than in young rats. On the other hand, the effects of chelation therapy on Ca, Cu, Fe. Mg, Mn and Zn tissue concentrations of Al-loaded rats were rather limited in both age groups. Conclusion: According to the present results, no remarkable negative effects on the tissue distribution of a number of essential elements would be expected if the above chelating agents were used for Al mobilization and removal.