Document Detail

Chronic valproate administration produces hepatic dysfunction and may delay brain maturation in infant mice.
MedLine Citation:
PMID:  6791049     Owner:  NLM     Status:  MEDLINE    
Infant mice (2 to 4 days old) received valproate (100 or 200 mg per kilogram body weight) subcutaneously once daily for 5 days. Both dosages decreased plasma beta-hydroxybutyrate levels to about one-third of the control value, in the face of normal free fatty acid and glycerol levels. At 200 mg per kilogram of valproate, there were significant decreases in brain weight and brain K content. Both doses produced metabolite changes in brain compatible with a reduced metabolic flux through the glycolytic pathway and the citric acid cycle. Valproate reduced brain aspartate but did not increase brain GABA levels in infant mice. At 200 mg per kilogram of valproate, brain glutamate decreased and taurine levels increased. Two hundred milligrams per kilogram of valproate caused a profound reduction of liver glycogen stores. The apparent decrease in cerebral metabolic rate, reduced glutamate and aspartate, and increased levels of taurine in brain may relate to the anticonvulsant action of valproate. Together with the decreased brain weight and K content, the findings are also compatible with maturational delay. Decreased ketonemia and liver glycogen content may relate to the hepatic toxicity associated with valproate administration in infants and children.
J H Thurston; R E Hauhart; D W Schulz; E F Naccarato; W E Dodson; J E Carroll
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurology     Volume:  31     ISSN:  0028-3878     ISO Abbreviation:  Neurology     Publication Date:  1981 Sep 
Date Detail:
Created Date:  1981-10-29     Completed Date:  1981-10-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1063-9     Citation Subset:  AIM; IM    
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MeSH Terms
3-Hydroxybutyric Acid
Amino Acids / metabolism
Animals, Newborn / metabolism*
Blood Glucose / analysis
Brain / anatomy & histology,  metabolism*
Hydroxybutyrates / blood
Liver / metabolism*
Liver Glycogen / metabolism
Organ Size / drug effects
Valproic Acid / adverse effects,  metabolism,  pharmacology*
Grant Support
Reg. No./Substance:
0/Amino Acids; 0/Blood Glucose; 0/Hydroxybutyrates; 0/Liver Glycogen; 300-85-6/3-Hydroxybutyric Acid; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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