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Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.
MedLine Citation:
PMID:  24442146     Owner:  NLM     Status:  Publisher    
Aim:To investigate the potential interactive effects of a high-fat diet (HFD) and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats.Methods:Male SD rats were orally administered VPA (100 or 500 mg·kg(-1)·d(-1)) combined with HFD or a standard diet for 8 weeks. Blood and liver samples were analyzed to determine lipid levels and hepatic function biomarkers using commercial kit assays. Low-molecular-weight compounds in serum, urine and bile samples were analyzed using a metabonomic approach based on GC/TOF-MS.Results:HFD alone induced extensive hepatocyte steatosis and edema in rats, while VPA alone did not cause significant liver lesions. VPA significantly aggravated HFD-induced accumulation of liver lipids, and caused additional spotty or piecemeal necrosis, accompanied by moderate infiltration of inflammatory cells in the liver. Metabonomic analysis of serum, urine and bile samples revealed that HFD significantly increased the levels of amino acids, free fatty acids (FFAs) and 3-hydroxy-butanoic acid, whereas VPA markedly decreased the levels of amino acids, FFAs and the intermediate products of the tricarboxylic acid cycle (TCA) compared with the control group. HFD aggravated VPA-induced inhibition on lipid and amino acid metabolism.Conclusion:HFD magnifies VPA-induced impairment of mitochondrial β-oxidation of FFAs and TCA, thereby increases hepatic steatosis and hepatotoxicity. The results suggest the patients receiving VPA treatment should be advised to avoid eating HFD.
Li-Fang Zhang; Ling-Sheng Liu; Xiao-Man Chu; Hao Xie; Li-Juan Cao; Cen Guo; Ji-Ye A; Bei Cao; Meng-Jie Li; Guang-Ji Wang; Hai-Ping Hao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-20
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  -     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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