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 (deferiprone) on urinary aluminum excretion and the aluminum level in tissues and serum of New Zealand rabbits was assayed. Twenty-seven rabbits 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 deprived of food for 24 hours and were given deferiprone intragastrically 3 hours after saline infusion. The urine was collected hourly for the next 6 hours for the later aluminum analysis. In the second stage, the other half of Al-only and DE2 + Al rabbits were given deferiprone 750 mu mol/kg/day intragastrically for 7 days. At the 35th day the animals were sacrificed and the selected organs were taken. The aluminum was determined 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 aluminum in the brain was not found to be altered. From the present study it appears that deferiprone is a highly orally effective aluminum chelator which may be the best in treating aluminum accumulation and toxicity.