Effects of monoisoamyl meso-2,3-dimercaptosuccinate on arsenite-induced maternal and developmental toxicity in mice.
The therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), on arsenite-induced maternal and developmental toxicity was evaluated in the pregnant mouse. Sodium arsenite (12 mg/kg) was intraperitoneally injected into Swiss mice on day 9 of gestation, whereas Mi-ADMS was given subcutaneously at 0.25, 5, 24, and 48 hr after arsenite exposure. Amelioration by Mi-ADMS of arsenite-induced maternal and embryofetal toxicity was assessed at 23.8, 47.5, and 95 mg/kg/day. Controls received 0.9% saline with or without arsenite. Cesarean sections were performed on gestation day 18. In the positive control group (treated with arsenite only), 20.8% of the pregnant animals died, whereas 37.5% of the dams were carrying completely resorbed litters. No arsenite-induced maternal lethality was seen following treatment with Mi-ADMS at 23.8, 47.5 and 95 mg/kg/day. Also, administration of the drug at these doses significantly reduced the embryolethality, as well as the incidence of some skeletal variations provoked by sodium arsenite. Although based on these findings, Mi-ADMS might be suggested as a potential antidote to prevent the arsenite-induced maternal and developmental toxicity, due to their reduced toxicity compared to Mi-ADMS, DMSA and DMPS would probably be more advisable for pregnant women exposed to arsenite.
Domingo
J L
JL
Laboratory of Toxicology and Biochemistry, School of Medicine, Rovira i Virgili University, Reus, Spain.
Gómez
M
M
Sánchez
D J
DJ
Llobet
J M
JM
Jones
M M
MM
Singh
P K
PK
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002614:Chelating Agents / Q000633:toxicity*; D005260:Female; D007279:Injections, Subcutaneous; D008425:Maternal Behavior / Q000187:drug effects*; D008429:Maternal Welfare; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D004113:Succimer / Q000031:analogs & derivatives* / Q000633:toxicity; D013997:Time Factors
D018053:Arsenites; D002614:Chelating Agents; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; C015001:arsenite