Methylmercury removal in the dog during infusion of 2,3-dimercaptosuccinic acid (DMSA).
2,3-Dimercaptosuccinic acid (DMSA) has been utilized in chelation therapy and in extracorporal complexing hemodialysis therapy for experimental methylmercury intoxication. In the latter application, substantial excretion of methylmercury occurred by the urinary route. This prompted the current study of the effects of continuous intravenous DMSA infusion therapy on methylmercury kinetics in the dog. Animals previously dosed with 203Hg-labeled methylmercury at 2.5 mg Hg/kg received a priming dose of DMSA, followed by a continuous iv infusion at dose rates that resulted in DMSA concentrations in plasma similar to those observed during DMSA complexing hemodialysis therapy. The kinetics of 203Hg removal in DMSA-infused dogs was compared with both saline-infused controls and DMSA complexing hemodialysis treated dogs. DMSA infusion therapy resulted in a shift in 203Hg binding within systemic blood from the red-cell fraction into plasma. This was consistent with an observed association of DMSA with the plasma fraction. The shift in 203Hg from red cells into plasma was paralleled by an increase in urinary clearance of 203Hg during the DMSA infusion period. In four dogs treated in this fashion, an average of 6.5 micrograms of mercury was removed by the urinary route over the 5-h treatment period, compared to 0.007 micrograms in the saline-infused dogs. Although a similar magnitude of mercury output into urine was observed during DMSA complexing hemodialysis, an additional 5 micrograms was removed by the dialyzer, making that technique 1.5 times as effective as infusion therapy. Comparing 203Hg tissue concentration after DMSA infusion therapy with the saline-treated controls revealed a 6.5-fold decrease in liver, a 3-fold reduction in kidney, and a 27% reduction in cerebrum. No significant differences were observed in medulla or cerebellum. Histopathology revealed no consistent differences between DMSA-treated and saline-treated animals. The DMSA infusion therapy was effective in causing a rapid removal of 203Hg from animals previously dosed with 203Hg-labeled methylmercury. DMSA infusion therapy may provide a useful therapeutic alternative for methylmercury poisoning when rapid removal of the intoxicant is desired and hemodialysis equipment and expertise are not readily available.
D000818:Animals; D004285:Dogs; D007700:Kinetics; D008628:Mercury / Q000378:metabolism; D008630:Mercury Poisoning / Q000188:drug therapy; D008657:Metabolic Clearance Rate; D008767:Methylmercury Compounds / Q000378:metabolism*; D004113:Succimer / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; D004113:Succimer; D008628:Mercury