Assessment of the protective activity of monisoamyl meso-2,3-dimercaptosuccinate against methylmercury-induced maternal and embryo/fetal toxicity in mice.
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.
Bellés
M
M
Laboratory of Toxicology and Biochemistry, School of Medicine, Rovira i Virgili University, Reus, Spain.
Sánchez
D J
DJ
Gómez
M
M
Domingo
J L
JL
Jones
M M
MM
Singh
P K
PK
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015913:Chelation Therapy; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D011247:Pregnancy; D004113:Succimer / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D002614:Chelating Agents; D008767:Methylmercury Compounds; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer