Domingo J L, Bosque M A, Piera V
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Fundam Appl Toxicol. 1991 Aug;17(2):314-20. doi: 10.1016/0272-0590(91)90221-o.
meso-2,3-Dimercaptosuccinic acid (DMSA), an antidote for the treatment of experimental and human poisoning by a number of heavy metals, has been reported to reduce the lethality of animals poisoned with arsenic more effectively than 2,3-dimercaptopropanol. In the present study, the effect of DMSA on arsenite-induced embryotoxic and teratogenic effects was evaluated in mice. In a first experiment, a series of four DMSA injections was administered sc to pregnant Swiss mice immediately after a single ip injection of 12 mg/kg of sodium arsenite (NaAsO2) given on Day 10 of gestation, and at 24, 48, and 72 hr thereafter. DMSA effectiveness was assessed at dosage levels of 0, 80, 160, and 320 mg/kg/day. Treatment with DMSA significantly reduced the embryolethality and the incidence of gross external and skeletal malformations and variations provoked by NaAsO2. Based on these findings, the effect of increasing the time interval between acute arsenite exposure and initiation of DMSA therapy was investigated in a second experiment. On Day 10 of gestation, DMSA (320 mg/kg) was administered sc to pregnant mice at 0, 0.25, 0.50, 1, 4, or 12 hr after a 12-mg/kg ip dose of NaAsO2. Embryotoxicity and teratogenicity derived from NaAsO2 exposure were significantly reduced when DMSA was given during the first hour after NaAsO2 injection. According to these results, a delay between acute arsenite intoxication and DMSA treatment should be avoided to have a practical beneficial effect on the arsenite exposed conceptus.
中-2,3-二巯基丁二酸（DMSA）是用于治疗多种重金属所致实验性中毒和人类中毒的解毒剂，据报道，它比2,3-二巯基丙醇能更有效地降低砷中毒动物的致死率。在本研究中，评估了DMSA对亚砷酸盐诱导的小鼠胚胎毒性和致畸性的影响。在第一个实验中，妊娠第10天腹腔注射12 mg/kg亚砷酸钠（NaAsO₂）后，立即给妊娠的瑞士小鼠皮下注射一系列4次DMSA，并在之后的24、48和72小时各注射一次。DMSA的有效性在0、80、160和320 mg/kg/天的剂量水平下进行评估。DMSA治疗显著降低了由NaAsO₂引起的胚胎致死率以及明显的外部和骨骼畸形及变异的发生率。基于这些发现，在第二个实验中研究了增加急性亚砷酸盐暴露与开始DMSA治疗之间的时间间隔的影响。在妊娠第10天，给妊娠小鼠腹腔注射12 mg/kg NaAsO₂后，分别在0、0.25、0.50、1、4或12小时皮下注射DMSA（320 mg/kg）。当在注射NaAsO₂后的第一小时内给予DMSA时，由NaAsO₂暴露引起的胚胎毒性和致畸性显著降低。根据这些结果，应避免急性亚砷酸盐中毒与DMSA治疗之间出现延迟，以便对暴露于亚砷酸盐的胚胎产生实际的有益影响。
