Comparative aluminium mobilizing actions of several chelators in aluminium-loaded uraemic rats

The relative effectiveness of deferoxamine (DFO), 1,2-dimethyl-1,3-hydroxypyrid-4-one (L1), and citric and succinic acids in mobilizing and promoting excretion of aluminium (Al) were compared in female uraemic rats which had previously received aluminium nitrate nonahydrate i.p. in a daily dose of 45 mg kg-1 for 3 weeks (5 days/week). Chelators were administered s.c. at doses equal to one-eighth of their respective LD50 for five days. L1 was also given p.o. in doses of 200 mg kg-1 day-1. Total urines were collected 24 h after each chelator administration. Total urinary Al excreted over the 5-day period, expressed as mg kg-1, were: controls, 3.4; DFO-treated, 4.5 (P < 0.05); citric acid-treated, 3.7; and succinic acid-treated, 2.7. Although the daily amounts of Al excreted into urine by L1-treated rats were significantly higher (P < 0.001) than those of the controls, most animals died during the period of treatment. Measurements of Al in selected tissues 24 h after the last administration of each chelator revealed that none of the compounds significantly altered the Al concentration in bone, kidney, and brain, whereas only DFO and succinic acid significantly reduced the levels of Al in spleen. Moreover, L1 (given s.c. or p.o.) and citric acid treatment led to a significant reduction in the liver Al burden. These results indicate the need for further investigations to determine the toxicity and the therapeutical safety margins of L1.