Teratogenic effects of vigabatrin in TO mouse fetuses

Yousef M. Abdulrazzaq, Salim M.A. Bastaki, R. Padmanabhan

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Vigabatrin (VGB) is a relatively recently introduced antiepileptic drug that enhances the brain levels of gamma aminobutyric acid (GABA). Few data on its teratogenic effects appear to have been reported. Our objective was to determine if VGB was teratogenic in the TO mouse. Single doses of 300-600 mg/kg of VGB dissolved in saline were administered intraperitoneally (IP) to groups of TO mice on one of gestation days (GD) 7-12. The controls were saline treated or untreated. No maternal toxic effects were observed in the 300 or 450 mg/kg groups, and the 600 mg/kg dose was totally lethal to the mothers. Fetuses were collected on GD 18. Both 300 and 450 mg/kg doses induced a consistently significant intrauterine growth retardation irrespective of the developmental stage at administration. VGB did not augment the spontaneous incidence of neural tube defects characteristic of this strain, but accelerated destruction of the brain in spontaneous exencephalic embryos. Mandibular and maxillary hypoplasia, arched palate, cleft palate (two cases), limb defects (one case), and exomphalos were observed in the malformed fetuses. The high incidence of exomphalos appears to be a unique result of VGB treatment. Alizarin red-S/alcian blue-stained skeletons revealed hypoplasia of mid facial bones, stage-dependent increase in the frequency of cervical and lumbar ribs, rib fusion, and sternal and vertebral malformations in the drug-treated fetuses. Middle and distal phalanges of the forepaw and mid phalanges and tarsals of the hindpaw failed to ossify in a significant number of experimental fetuses. Homeotic shift in terms of presacral vertebral number and a high incidence of lumbar and cervical ribs in the treated group are suggestive of treatment-related alterations in gene expression. In view of the paucity of human and animal data on the reproductive toxicologic effects of VGB, the results of the present study assume particular importance and suggest that VGB should be used in pregnancy with extreme caution.

Original languageEnglish
Pages (from-to)165-176
Number of pages12
JournalTeratology
Volume55
Issue number3
DOIs
Publication statusPublished - Mar 1997

ASJC Scopus subject areas

  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'Teratogenic effects of vigabatrin in TO mouse fetuses'. Together they form a unique fingerprint.

Cite this