✦ LIBER ✦

Myo-inositol enhances teratogenicity of valproic acid in the mouse

✍ Scribed by Valentina Massa; Bogdan Wlodarczyk; Erminio Giavini; Richard H. Finnell

Publisher: John Wiley and Sons
Year: 2006
Tongue: English
Weight: 102 KB
Volume: 76
Category: Article
ISSN: 1542-0752
DOI: 10.1002/bdra.20228

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

BACKGROUND

Valproic acid (VPA) is an anticonvulsant drug that is widely used therapeutically for a variety of neurological conditions. VPA is also well known for its teratogenic potential in both humans and experimental animal models. The typical malformations observed following VPA exposure include neural tube defects (NTDs) and craniofacial and skeletal malformations. Nevertheless, the mechanisms underlying VPA's anticonvulsant efficacy or its teratogenicity remain to be elucidated. It was recently suggested that a relationship exists between VPA exposure and the cellular depletion of myo‐inositol (INO). Furthermore, INO has been shown to rescue NTDs in the curly tail mouse. The aim of this study was to investigate the interactions of VPA and INO in the developing embryo.

METHODS

For this purpose, 2 strains of mice were used: SWV/Fnn (known to be sensitive to VPA) and LM/Bc (known to be resistant to VPA‐induced NTDs). Pregnant females were randomly assigned to 4 experimental groups: control, VPA (600 mg/kg), INO (400 mg/kg), and VPA plus INO. VPA was injected IP at 8.5 days postcoitum (dpc). INO was administered PO twice a day from 6.5 to 10.5 dpc. At term the dams were killed, the uteri were removed, and all of the general toxicological parameters (number of implants, resorptions, dam weight, and fetus weight) were recorded and statistically analyzed.

RESULTS

Postimplantation loss in the SWV/Fnn strain and NTDs in the LM/Bc strain were significantly increased after the coadministration of VPA and INO.

CONCLUSIONS

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