succimer and Fetal-Death

Topics: Abnormalities, Drug-Induced; Animals; Arsenic Poisoning; Arsenicals; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Female; Fetal Death; Infusions, Parenteral; Methylation; Mice; Pregnancy; Succimer

The protective activity of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), a new monoester of 2,3-dimercaptosuccinic acid (DMSA), on methylmercury-induced maternal and developmental toxicity was assessed in mice. A series of four Mi-ADMS injections was given s.c. at 0.25, 6, 24, and 48 h after oral administration of 25 mg/kg of methylmercury chloride (MMC) given on day 10 of gestation. Mi-ADMS effectiveness was tested at 0, 23.8, 47.6 and 95 mg/kg. Cesarean sections were performed on gestation day 18. All live fetuses were examined for external, internal, and skeletal abnormalities. Oral MMC administration resulted in an increase in the number of resorptions, and a decrease in fetal body weight, whereas the incidence of cleft palate, micrognathia, and skeletal variations was also increased in the fetuses of the MMC-treated groups. Although significant amelioration of MMC-induced embryolethality by Mi-ADMS was not noted at any dose, MMC-induced fetotoxicity was reduced by administration of this agent at 23.8, 47.6, and 95 mg/kg. However, the intrinsic toxicity of Mi-ADMS would be a restrictive factor for the possible therapeutic use of this chelator in pregnant women exposed to organic mercury.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Chelating Agents; Chelation Therapy; Disease Models, Animal; Embryonic and Fetal Development; Female; Fetal Death; Male; Methylmercury Compounds; Mice; Pregnancy; Succimer

Methyl mercury has been reported to be embryotoxic and teratogenic in numerous systems such as fish, birds, and mammals. meso-2,3-Dimercaptosuccinic acid (DMSA) has been useful for prevention and treatment of mercury poisoning. In this study, the protective activity of DMSA on methyl mercury-induced embryo/fetotoxicity was evaluated in mice. A series of four DMSA injections was administered subcutaneously to pregnant Swiss mice immediately after oral administration of 25 mg/kg methyl mercury chloride (MMC) given on Day 10 of gestation, and at 24, 48, and 72 hr thereafter. DMSA effectiveness was tested at 0, 80, 160, and 320 mg/kg/day. Oral administration of MMC resulted in a high rate of resorptions and dead fetuses as well as a reduced fetal body weight. Moreover, cleft palate (46.9%) and various developmental variations were found in the positive control group. Treatment with DMSA at 160 and 320 mg/kg/day significantly decreased the embryolethality of MMC, whereas at 320 mg DMSA/kg/day the incidence of skeletal anomalies and cleft palate (2.8%) was also significantly reduced. According to these results, DMSA offers encouragement with regard to its therapeutic potential for pregnant women exposed to methyl mercury.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Evaluation, Preclinical; Embryonic and Fetal Development; Female; Fetal Death; Mercury Poisoning; Mice; Pregnancy; Succimer