meso-2,3-Dimercaptosuccinic acid and prevention of arsenite embryotoxicity and teratogenicity in the mouse.
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.
Domingo
J L
JL
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Bosque
M A
MA
Piera
V
V
D000818:Animals; D001151:Arsenic / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018053:Arsenites; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D051379:Mice; D011247:Pregnancy; D017670:Sodium Compounds; D004113:Succimer / Q000494:pharmacology*; D013723:Teratogens / Q000633:toxicity*
D018053:Arsenites; D017670:Sodium Compounds; D013723:Teratogens; C017947:sodium arsenite; D004113:Succimer; D001151:Arsenic