meso-2,3-dimercaptosuccinic acid monoalkyl esters: effects on mercury levels in mice.
Seven monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative activities in mobilizing and promoting excretion of mercury in mercury-laden mice. Compounds assessed were the ethyl (M-EDMS), n-propyl (Mn-PDMS), isopropyl (Mi-PDMS), n-butyl (Mn-BDMS), isobutyl (Mi-BDMS), n-amyl (Mn-ADMS), and isoamyl (Mi-ADMS) esters. 2,3-Dimercaptopropane-1-sulfonate (DMPS) and DMSA were used as positive controls. After the first oral dose of each compound at 0.5 mmol/kg, DMSA and DMPS reduced the corporal mercury burden 16% and 24%, respectively, compared to controls, while the monoesters effected reductions of 35% (M-EDMS) to 49% (Mi-ADMS). After the second treatment at the same dose, the respective reductions produced by DMSA and DMPS were 24% and 38%, and those conferred by the monoesters ranged from 52% (M-EDMS) to 61% (Mn-BDMS). Determination of the comparative dose-response relationships of DMSA and Mi-ADMS on corporal and renal mercury concentrations revealed the monoester to be more active than DMSA on both parameters at each dose used. The cumulative amount of mercury excreted in urine by control mice over a 3-day period was 7.08 micrograms; this was increased 22%, 85%, and 94% by daily i.p. injections of DMSA, DMPS, and Mi-ADMS, respectively, at a daily dose of 0.1 mmol/kg. The respective cumulative 3-day totals recovered in feces from control mice and from mice treated with DMSA, DMPS, and Mi-ADMS were 9.76, 8.21, 10.44, and 11.73 micrograms. Parallel daily measurements of retained whole body radioactivity from 203Hg in mice were in good agreement with the values calculated from the excretion data.
Gale
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GR
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC.
Smith
A B
AB
Jones
M M
MM
Singh
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PK
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004952:Esters; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics* / Q000652:urine; D008630:Mercury Poisoning / Q000188:drug therapy*; D051379:Mice; D004113:Succimer / Q000494:pharmacology* / Q000627:therapeutic use; D014494:Unithiol / Q000494:pharmacology / Q000627:therapeutic use
D004952:Esters; D014494:Unithiol; D004113:Succimer; D008628:Mercury