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Lack of teratogenicity of trans-2-ene-valproic acid compared to valproic acid in rats. 1991

C V Vorhees, and K D Acuff-Smith, and W P Weisenburger, and D R Minck, and J S Berry, and K D Setchell, and H Nau
Institute for Developmental Research, Children's Hospital Research Foundation, Cincinnati, Ohio 54229-2899.

The teratogenicity of trans-2-ene-valproic acid (300 and 400 mg/kg) was compared with that of valproic acid (VPA; 300 mg/kg) and controls (corn oil) administered by gavage to Sprague-Dawley CD rats on embryonic (E) days 7-18. At the 300 mg/kg dose, trans-2-ene-VPA produced no change in maternal weight, number of implantations, proportion of resorptions, proportion of malformations, or fetal weight. By contrast, the same dose of VPA (300 mg/kg) reduced maternal weight during gestation, increased malformations (12.0% vs. 0.7% in controls), and reduced fetal body weight by 25.1%. An even higher dose of trans-2-ene-VPA (400 mg/kg) produced a reduction in maternal body weight during treatment and reduced fetal body weight (by 7.9%), but did not increase resorptions or malformations in the fetuses. On day E18, maternal serum drug concentrations of VPA were higher in the VPA-treated group compared with those of trans-2-ene-VPA in the trans-2-ene-VPA-treated groups at 1 hr posttreatment. At 6 hr posttreatment the reverse was seen. trans-2-ene-VPA may be absorbed more rapidly and distributed differently than VPA. Overall, the data support the view that trans-2-ene-VPA at equal or higher doses than VPA is not teratogenic in rats.

UI MeSH Term Description Entries
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
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
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
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
D005229 Fatty Acids, Monounsaturated Fatty acids which are unsaturated in only one position. Monounsaturated Fatty Acid,Acid, Monounsaturated Fatty,Acids, Monounsaturated Fatty,Fatty Acid, Monounsaturated,Monounsaturated Fatty Acids
D005260 Female Females
D005314 Embryonic and Fetal Development Morphological and physiological development of EMBRYOS or FETUSES. Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
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
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen

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