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Involvement of fatty acid metabolism in the hepatotoxicity induced by divalproex sodium.
MedLine Citation:
PMID:  22531971     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Divalproex sodium is an antiepileptic drug. Hepatotoxicity is one of the most common side effects induced by divalproex sodium. Impaired fatty acid metabolism is considered to play an important role in the drug-induced hepatotoxicity. The sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor α (PPARα) are two key transcription factors involved, respectively, in fatty acid synthesis and degradation in liver. In the present study, we investigated the hepatotoxicity induced by divalproex sodium and its potential mechanism. The results indicated that divalproex sodium significantly decreased the cell viability and increased lactate dehydrogenase leakage in hepatocytes. The activities of alanine aminotransferase and aspartate transaminase were increased in hepatocytes treated with divalproex sodium. Furthermore, divalproex sodium activated SREBP-1c and increased the mRNA expressions of acetyl-CoA carboxylase 1, fatty acid synthase and stearoyl-CoA desaturase 1. Divalproex sodium also inhibited PPARα and decreased the messenger RNA expressions of 3-hydroxy-3-methylglutaryl-CoA synthase 2 and carnitine palmitoyltransferase 1A. These results suggest that the hepatotoxicity induced by divalproex sodium may be related with fatty acid synthesis and degradation mediated by SREBP-1c and PPARα in hepatocytes.
Authors:
W Wang; R Lin; J Zhang; Y Mao; X Bu; Q Ji; X Zhai; Q Lin; L Yang; K Zhang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-24
Journal Detail:
Title:  Human & experimental toxicology     Volume:  -     ISSN:  1477-0903     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9004560     Medline TA:  Hum Exp Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Xi'an Jiaotong University, China.
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