Marked accumulation of valproic acid in embryonic neuroepithelium of the mouse during early organogenesis

Journal Article · Fri Jun 01 04:00:00 EDT 1990 · Teratology; (USA)

DOI:https://doi.org/10.1002/tera.1420410606· OSTI ID:6718783

Dencker, L; Nau, H; D'Argy, R ^[1]

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1. Univ. of Uppsala (Sweden)

Valproic acid, an antiepileptic drug, causes neural tube defects in mice and man. 14C-labeled valproic acid (sodium-salt) was administered to pregnant mice on days 8 and 9 of gestation (period of high sensitivity in regard to formation of neural tube defects in this species). Two dose levels of valproic acid (1 and 400 mg/kg) were used; in each case the total radioactivity administered was the same: 400 microCi/kg or 14.7 MBq/kg. Autoradiography combined with computerized densitometry revealed that in low-dose animals most of the radioactivity was confined to maternal liver and kidney, while at high doses more activity was observed in soft tissues and fluids, including amniotic fluid. In the embryo, the neuroepithelium showed the highest concentration, irrespective of dose and survival interval (30 min, 3 h, and 6 h). Upon administration of the high dose, up to five times more radioactivity (approximately 2,000 times more valproic acid) was recovered in embryonic tissues than after the low dose. It is concluded that high doses of VPA saturate the capacities of metabolism, excretion, and protein binding in the maternal organism, resulting in a higher proportion of the dose reaching the embryo, allowing more of the drug to be accumulated by the target organ, the neuroepithelium.

• OSTI ID: 6718783
• Journal Information: Teratology; (USA), Journal Name: Teratology; (USA) Vol. 41:6; ISSN 0040-3709; ISSN TJADA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
ANTICONVULSANTS
AUTORADIOGRAPHY
BIOLOGICAL ACCUMULATION
BODY
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DIGESTIVE SYSTEM
DRUGS
EMBRYOS
EPITHELIUM
GLANDS
KIDNEYS
LABELLED COMPOUNDS
LIVER
MAMMALS
MICE
NERVOUS SYSTEM
ONTOGENESIS
ORGANS
PREGNANCY
RODENTS
TERATOGENESIS
TISSUES
VERTEBRATES