Combined treatment withracemic-DMSA and EDTA for lead mobilization in rats

Female rats were loaded with lead acetate (5 mg Pb/kg) during 2 weeks (10 times) intraperitoneally. Four-day chelation treatment started 1 week later with CaNa2 ethylenediaminetetraacetate (EDTA, 0.3 mmol/kg i.p. at 4:00 p.m.), and meso- or racemic-2,3-dimercaptosuccinic acid (meso- or rac-DMSA, 0.5 mmol/kg p.o. at 10:00 a.m.). One group was administered EDTA as monotherapy, and two groups received combined treatment with EDTA plus either meso-DMSA or rac-DMSA. Lead was determined in femur, kidneys, and brain. Urinary eliminations of lead, iron, zinc, and copper were also evaluated. With EDTA monotherapy, lead was reduced in kidneys. Combined treatment with EDTA plus meso-DMSA reduced lead in kidneys and brain, and EDTA plus rac-DMSA treatment reduced lead in femur, kidneys, and brain. Urine lead elimination was increased by EDTA monotherapy 10 times, and by both combined treatments 14–15 times. Urine zinc excretion was increased by both EDTA monotherapy and in combined treatment with meso-DMSA 3–4 times, and in combined treatment with rac-DMSA 5–6 times. Both combined treatments increased copper urinary excretion 3–4 times. Best results in reducing tissue lead were obtained when EDTA therapy was combined with rac-DMSA treatment. Since this combination also caused highest urinary trace element elimination, more data are needed before recommending rac-DMSA for use in combined treatment of lead poisoning. J. Trace Elem. Exp. Med. 13:277–284, 2000.