INFLUENCE OF THE CHELATOR 1,2-DIMETHYL-3-HYDROXYPYRID-4-ONE ON ALUMINUM ELIMINATION IN ALUMINUM-LOADED RABBITS

The effect of the chelator agent 1,2-dimethyl-3-hydroxypyrid-4-one (de feriprone) on urinary aluminum excretion and the aluminum level in tis sues and serum of New Zealand rabbits was assayed. Twenty-seven rabbit s were randomly divided into 4 groups: control, Al-only, DE1 + Al, DE2 + Al. Aluminum-loaded rabbits were treated with 600 mu mol Al/kg/day s.c. far 2 weeks. The test began two days after the last injection. In the first stage, half of the Al-only and DE1 + Al rabbits were depriv ed of food for 24 hours and were given deferiprone intragastrically 3 hours after saline infusion. The urine was collected hourly for the ne xt 6 hours for the later aluminum analysis. In the second stage, the o ther half of Al-only and DE2 + Al rabbits were given deferiprone 750 m u mol/kg/day intragastrically for 7 days. At the 35th day the animals were sacrificed and the selected organs were taken. The aluminum was d etermined by AAS. Results showed that deferiprone could significantly increase urinary aluminum excretion and mobilize aluminum stores from tissues to blood. The content of aluminum of bone and kidney in DE2 Al rabbits was significantly lower than that in Al-only rabbits. The a luminum in the brain was not found to be altered. From the present stu dy it appears that deferiprone is a highly orally effective aluminum c helator which may be the best in treating aluminum accumulation and to xicity.