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Effectiveness of Chelation Therapy with Time after Acute Uranium Intoxication

*Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona San Lorenzo 21, 43201-Reus
Department of Toxicology, School of Medicine, University of Barcelona Casanova 143, 08036-Barcelona, Spain
Received January 31, 1989; accepted June 8, 1989
Effectiveness of Chelation Therapy with Time after Acute Uranium Intoxication. DOMINGO, J. L, ORTEGA, A., LLOBET, J. M., AND CORBELLA, J. (1990). Fundam. Appl. Toxicol 14, 8895. The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-l,3-benzenedisulfonicacid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0,0.25, 1,4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0,0.25, or I hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.