| Vigabatrin (VGB) administered during late gestation lowers maternal folate concentration and causes pregnancy loss, fetal growth restriction and skeletal hypoplasia in the mouse. | |
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MedLine Citation:
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PMID: 20206253 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vigabatrin (VGB) has several therapeutic advantages over older antiepileptic drugs (AED), but there is a lack of information about its potential reproductive toxicologic effects. Our aim was to evaluate the consequences of VGB administered during late gestation on fetal growth and development in the mouse. Based on the results of our previous study, we administered groups of mice a single dose of 450 mg/kg VGB on one of gestation days (GD) 15, 16 or 17. Fetuses were collected on GD 18. VGB groups had a significant incidence of fetal death, abortion, intrauterine growth restriction (IUGR), and hypoplasia of the axial skeleton, metacarpals, metatarsal and phalanges. Abortion was characterized by visible hemorrhagic expulsion of the embryos with their membranes. Maternal plasma folate (FA) and vitamin B12 concentrations were found to be markedly reduced within 12h of VGB treatment. Mice were supplemented with FA from GD 12 through GD 17 with or without a single dose of VGB on GD 15. This group had no abortions. Their fetuses had better body weight and lower frequency of IUGR than those of the non-supplemented VGB group. These data suggest that reductions in maternal FA and vitamin B12 concentrations play an important role in fetal loss, IUGR and skeletal hypoplasia induced by VGB during late gestation in the mouse. In view of the finding that a significant maternal toxicity is associated with this dose regimen, additional groups of mice were treated with 350 mg/kg VGB during embryogenesis and late gestation. This treatment was found to be maternally nontoxic. However, this low dose also resulted in significant fetal loss and IUGR when treatment occurred during late gestation. These data support the hypothesis that late gestation is particularly susceptible to VGB-induced fetal loss and IUGR in the mouse. |
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Authors:
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R Padmanabhan; Y M Abdulrazzaq; S M A Bastaki; M Nurulain; M Shafiullah |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-03 |
Journal Detail:
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Title: Reproductive toxicology (Elmsford, N.Y.) Volume: 29 ISSN: 1873-1708 ISO Abbreviation: Reprod. Toxicol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-16 Completed Date: 2010-07-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8803591 Medline TA: Reprod Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 366-77 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Basic Medical Sciences, The Mercer University School of Medicine, Macon, GA 31207, USA. rengasamy p@mercer.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticonvulsants* / adverse effects, pharmacology Bone and Bones Dietary Supplements Embryonic Development / drug effects Female Fetal Development / drug effects* Fetal Growth Retardation / chemically induced Fetus Folic Acid / adverse effects, pharmacology Mice Mice, Inbred Strains Musculoskeletal System Pregnancy Reproduction Stillbirth Vigabatrin* / adverse effects, pharmacology Vitamin B 12 / adverse effects, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 59-30-3/Folic Acid; 60643-86-9/Vigabatrin; 68-19-9/Vitamin B 12 |
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