Determination and metabolism of dithiol chelating agents. XV. The meso-2,3-dimercaptosuccinic acid-cysteine (1:2) mixed disulfide, a major urinary metabolite of DMSA in the human, increases the urinary excretion of lead in the rat.
Meso-2,3-dimercaptosuccinic acid (DMSA) in humans is an effective p.o. therapeutically useful chelating agent of Pb. In humans given DMSA p.o., the major urinary metabolite is DMSA-cysteine (1:2) mixed disulfide. In order to determine its efficacy in mobilizing Pb and increasing urinary Pb excretion, the mixed disulfide was given to rats treated previously with Pb acetate. The mixed disulfide was as effective as DMSA in increasing the urinary excretion of Pb and mobilizing Pb from the kidney. DMSA, however, appears to be superior for mobilizing Pb from the liver and the brain. After the mixed disulfide was given s.c. to rats, DMSA was found in the blood and urine. Twenty-four hours after administration, 0.7% of the administered mixed disulfide was found in the urine as DMSA, indicating the mixed disulfide can be reduced to DMSA. The mixed disulfide was also reduced in vitro to DMSA during incubation with rat blood. Although in the rat the DMSA-cysteine (1:2) mixed disulfide mobilized Pb from the kidney, increased the urinary excretion of Pb and was to some extent reduced to DMSA, its fate and pharmacological properties in the human, where it is found after DMSA administration, are unknown.
Maiorino
R M
RM
Department of Molecular and Cellular Biology, University of Arizona, Tucson.
Aposhian
M M
MM
Xu
Z F
ZF
Li
Y
Y
Polt
R L
RL
Aposhian
H V
HV
D000818:Animals; D001711:Biotransformation; D002614:Chelating Agents / Q000032:analysis / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007854:Lead / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D004113:Succimer / Q000031:analogs & derivatives* / Q000378:metabolism; D014018:Tissue Distribution
D002614:Chelating Agents; D007854:Lead; C084962:2,3-dimercaptosuccinic acid-cysteine (1-2) mixed disulfide; D004113:Succimer; D003545:Cysteine