Effects of meso-2,3-dimercaptosuccinic acid (DMSA) on methyl mercury-induced teratogenesis in mice.
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.
Sanchez
D J
DJ
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Gomez
M
M
Llobet
J M
JM
Domingo
J L
JL
D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D008630:Mercury Poisoning / Q000517:prevention & control*; D051379:Mice; D011247:Pregnancy; D004113:Succimer / Q000008:administration & dosage / Q000627:therapeutic use*
D004113:Succimer