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The sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) 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 PPAR\u03b1 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 PPAR\u03b1 in hepatocytes.<\/jats:p>","DOI":"10.1177\/0960327112444477","type":"journal-article","created":{"date-parts":[[2012,4,24]],"date-time":"2012-04-24T22:00:38Z","timestamp":1335304838000},"page":"1092-1101","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Involvement of fatty acid metabolism in the hepatotoxicity induced by divalproex sodium"],"prefix":"10.1177","volume":"31","author":[{"given":"W","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Key Laboratory of Environment and Genes Related to Diseases, School of Medicine, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, PR 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