Mobilization of lead over the course of DMSA chelation therapy and long-term efficacy.
An increasing number of factors suggest that a reevaluation of the current use of CaNa2EDTA for elevated Pb body burden is advisable and, further, emphasize the need for alternative safe and efficacious chelating agents. One candidate that appears to have potential is meso-2,3-dimercaptosuccinic acid (DMSA). However, little is known about the pattern of Pb mobilization or redistribution produced by this chelator or about its long-term efficacy, issues that were examined in this study. After a 3- to 4-month exposure to 50 ppm of Pb acetate in drinking water, different groups of rats received an i.p. injection of saline or 25 or 50 mg/kg of DMSA once a day for either 1, 2, 3, 4 or 5 days and were sacrificed 24 hr after the final injection. To assess long-term efficacy of the chelator, an additional group of rats received five injections (one per day) of 50 mg/kg of DMSA and were sacrificed 4 months later. Tissue analyses indicated that DMSA mobilized Pb only from soft tissue, with no loss noted from femur and consequently no observable redistribution of Pb. Large decrements in blood, brain and kidney Pb concentrations were noted, with a delayed loss from liver. The effects were not sustained, however, when assessed 4 months later. With respect to redistribution of mobilized Pb to critical organs and magnitude of decline in soft tissue Pb concentration, DMSA appears to be a safe and particularly effective chelator and thus may be a viable alternative to CaNa2EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Cory-Slechta
D A
DA
Department of Biophysics, University of Rochester, School of Medicine and Dentistry, New York.
D000704:Analysis of Variance; D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D007854:Lead / Q000493:pharmacokinetics*; D007855:Lead Poisoning / Q000188:drug therapy*; D051381:Rats; D004113:Succimer / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*; D013997:Time Factors; D014018:Tissue Distribution
D002614:Chelating Agents; D013438:Sulfhydryl Compounds; D007854:Lead; D004113:Succimer