View : 15 Download: 0

Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

Title
Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver
Authors
Lee M.-H.Kim M.Lee B.-H.Kim J.-H.Kang K.-S.Kim H.-L.Yoon B.-I.Chung H.Kong G.Lee M.-O.
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2008
Journal Title
Toxicology and Applied Pharmacology
ISSN
0041-008XJCR Link
Citation
vol. 226, no. 3, pp. 271 - 284
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P < 0.05) and fold change (> 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity. © 2007 Elsevier Inc. All rights reserved.
DOI
10.1016/j.taap.2007.09.014
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE