ArticleActa pharmacologica Sinica2014
Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.
Article in Acta pharmacologica Sinica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 45 citations in OpenAlex.
- The Role of Sodium Valproate in Clozapine-Associated Cardiotoxicities: The Importance of Cellular and Systemic Energetics.Cardiovascular toxicology · 2026Review
- Integrated proteomics and metabolomics analyses reveal new insights into the antitumor effects of valproic acid plus simvastatin combination in a prostate cancer xenograft model associated with downmodulation of YAP/TAZ signaling.Cancer cell international · 2024Article
- Ethnic Aspects of Valproic Acid P-Oxidation.Biomedicines · 2024Review
- Micropatterned primary hepatocyte co-culture (HEPATOPAC) for fatty liver disease modeling and drug screening.Scientific reports · 2023Article
- Valproate-Induced Metabolic Syndrome.Biomedicines · 2023Review
- Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure-a study with valproic acid and 14 of its analogues.Archives of toxicology · 2022Article
- Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.International journal of molecular sciences · 2021Review
- Protective Effect of Thyme Honey against Valproic Acid Hepatotoxicity in Wistar Rats.BioMed research international · 2021Article
- Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae.Scientific reports · 2020Article
- Hepatic gene expression explains primary drug toxicity in bipolar disorder.Translational psychiatry · 2019Article
- NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.Scientific reports · 2019Article
- Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity.Frontiers in pharmacology · 2019Article
- Microphysiological flux balance platform unravels the dynamics of drug induced steatosis.Lab on a chip · 2018Article
- Role of xenobiotics in the induction and progression of fatty liver disease.Toxicology research · 2018Review
- Study of Valproic Acid-Enhanced Hepatocyte Steatosis.BioMed research international · 2016Article
- Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease.BioMed research international · 2015Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the potential interactive effects of a high-fat diet (HFD) and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats.
methodsMale 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.
resultsHFD 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.
conclusionHFD 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.
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