Effects of sodium valproate and oxygen on the CD-1 mouse fetus

This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a t...

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Bibliographic Details
Published inJournal of craniofacial genetics and developmental biology Vol. 8; no. 1; p. 35
Main Authors Paulson, R B, Sucheston, M E, Hayes, T G, Weiss, H S, Sachs, L A, Oca, M, Kernan, B, Weiss, S
Format Journal Article
LanguageEnglish
Published Denmark 1988
Subjects
Animals
Female
Fetal Resorption
Fetus - drug effects
Hematoma - chemically induced
Hematoma - embryology
Hypoxia - physiopathology
Mice
Mice, Inbred Strains
Oxygen - toxicity
Pregnancy
Reference Values
Teratogens
Valproic Acid - blood
Valproic Acid - toxicity
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Summary:This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12. Dams were then exposed continuously to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments during gestation days 5-12, in order to determine if hyperoxic maternal conditions offered a protective environment for the fetus, and conversely, if hypoxia exacerbated teratogenicity. Dams were sacrificed on gestation day 18, and litter and fetal data were collected. It was determined in separate groups under normoxic conditions that the osmotic minipump system maintained VA plasma levels corresponding to human therapeutic levels. Sodium valproate was found to induce developmental toxicity in the CD-1 mouse fetus at human therapeutic drug plasma levels. Fetal weights were reduced, and the number of resorptions, deaths, and hematomas was increased. While hypoxia exacerbated the toxic effect on the fetus, hyperoxia failed to ameliorate the outcome.
ISSN:0270-4145