Gale G R, Smith A B, Jones M M, Singh P K
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC.
Toxicology. 1993 Jul 11;81(1):49-56. doi: 10.1016/0300-483x(93)90155-l.
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.
对七种内消旋-2,3-二巯基丁二酸（DMSA）单酯在含汞小鼠体内促进汞排出的相对活性进行了评估。所评估的化合物为乙酯（M-EDMS）、正丙酯（Mn-PDMS）、异丙酯（Mi-PDMS）、正丁酯（Mn-BDMS）、异丁酯（Mi-BDMS）、正戊酯（Mn-ADMS）和异戊酯（Mi-ADMS）。2,3-二巯基丙烷-1-磺酸盐（DMPS）和DMSA用作阳性对照。在以0.5 mmol/kg的剂量首次口服每种化合物后，与对照组相比，DMSA和DMPS分别使体内汞负荷降低了16%和24%，而单酯使汞负荷降低了35%（M-EDMS）至49%（Mi-ADMS）。在以相同剂量进行第二次治疗后，DMSA和DMPS产生的各自降低率分别为24%和38%，单酯产生的降低率范围为52%（M-EDMS）至61%（Mn-BDMS）。对DMSA和Mi-ADMS对体内和肾脏汞浓度的比较剂量反应关系的测定表明，在所用的每种剂量下，单酯在这两个参数上均比DMSA更具活性。对照小鼠在3天内尿中排出的汞累积量为7.08微克；通过每天腹腔注射0.1 mmol/kg的DMSA、DMPS和Mi-ADMS，分别使汞排出量增加了22%、85%和94%。对照小鼠以及用DMSA、DMPS和Mi-ADMS治疗的小鼠在粪便中回收的3天累积总量分别为9.76、8.21、10.44和11.73微克。对小鼠体内203Hg保留的全身放射性进行的平行每日测量结果与根据排泄数据计算的值高度一致。
