meso-2,3-Dimercaptosuccinic acid and prevention of arsenite embryotoxicity and teratogenicity in the mouse. 1991

J L Domingo, and M A Bosque, and V Piera
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.

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.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004113 Succimer A mercaptodicarboxylic acid used as an antidote to heavy metal poisoning because it forms strong chelates with them. DMSA,Dimercaptosuccinic Acid,2,3-Dimercaptosuccinic Acid,Butanedioic Acid, 2,3-Dimercapto-, (R*,S*)-Isomer,Chemet,Ro-1-7977,Succicaptal,Succimer Antimony Sodium Salt, (R*,S*)-Isomer,Succimer, (R*,R*)-(+,-)-Isomer,Succimer, Dipotassium Salt,Succimer, Disodium Salt,Succimer, Monosodium Salt,Succimer, Rhenium Salt,Succimer, Tin Salt,Tin Dimercaptosuccinate,meso-Dimercaptosuccinic Acid,2,3 Dimercaptosuccinic Acid,Acid, 2,3-Dimercaptosuccinic,Acid, Dimercaptosuccinic,Acid, meso-Dimercaptosuccinic,Dimercaptosuccinate, Tin,Dipotassium Salt Succimer,Disodium Salt Succimer,Monosodium Salt Succimer,Rhenium Salt Succimer,Ro 1 7977,Ro17977,Tin Salt Succimer,meso Dimercaptosuccinic Acid
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D005865 Gestational Age The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination. Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001151 Arsenic A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed) Arsenic-75,Arsenic 75
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen
D017670 Sodium Compounds Inorganic compounds that contain sodium as an integral part of the molecule. Compounds, Sodium
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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