CHELATION IN METAL INTOXICATION .37. EFFICACY OF COMBINED CHELATION IN LEAD-INTOXICATION

The combination of a bone lead mobilizer, viz., CaNa(2)EDTA, and a soft tissue depleter such as meso-2,3-dimercaptosuccinic acid (DMSA) or the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS) was investigated for its efficacy to enhance the excretion of lead, to reduce its body burden, and to reverse certain lead-induced biochemical alterations by either of them alone in rats. The administration of CaNa(2)EDTA or DMSA was more effective than that of DMPS, and the combination of CaNa(2)EDTA and DMSA was more efficient than that of CaNa(2)EDTA and DMPS or the individual chelators in enhancing urinary/fecal excretion of lead, in reducing hepatic, renal, and femur concentration of lead, and in restoring lead-induced inhibition of blood delta-aminolevulinic acid dehydratase and increase in blood zinc protoporphyrin and urinary delta-aminolevulinic acid levels. The brain lead was depleted by DMSA only, but the combined chelation failed to improve upon the ability of DMSA. However, chelation therapy increased diuresis and tissue depletion of zinc.