Dataset Information

Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.

ABSTRACT: To investigate the potential interactive effects of a high-fat diet (HFD) and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats.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.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.HFD magnifies VPA-induced impairment of mitochondrial ?-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.

SUBMITTER: Zhang LF

PROVIDER: S-EPMC4647887 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.

Zhang Li-fang LF Liu Ling-sheng LS Chu Xiao-man XM Xie Hao H Cao Li-juan LJ Guo Cen C A Ji-ye JY Cao Bei B Li Meng-jie MJ Wang Guang-ji GJ Hao Hai-ping HP

Acta pharmacologica Sinica 20140120 3

<h4>Aim</h4>To investigate the potential interactive effects of a high-fat diet (HFD) and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats.<h4>Methods</h4>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 ...[more]

PMID: 24442146

Similar Datasets

Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of metabolic syndrome and has attracted widespread attention due to its increased prevalence. Daily dietary management is an effective strategy for the prevention of NAFLD. Quinoa, a nutritious pseudocereal, is abundant in antioxidative bioactive phytochemicals. In the present study, the effects of different amounts of quinoa on the progression of NAFLD and the related molecular mechanism were investigated.MethodsMale SD rats were simultaneously administered a high fat diet (HF) and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, hepatic TG (triglyceride) and TC (total cholesterol) as well as serum antioxidative parameters were determined, and hematoxylin-eosin staining (H&E) staining was used to evaluate hepatic steatosis. Differential metabolites in serum and hepatic tissue were identified using UPLC-QTOF-MSE. The mRNA expression profile was investigated using RNA-Seq and further verified using real-time polymerase chain reaction (RT-PCR).ResultsLow amounts of quinoa (equivalent to 100 g/d of human intake) effectively controlled the weight of rats fed a high-fat diet. In addition, quinoa effectively inhibited the increase in hepatic TG and TC levels, mitigated pathological injury, promoted the increase in SOD and GSH-Px activities, and decreased MDA levels. Nontarget metabolic profile analysis showed that quinoa regulated lipid metabolites in the circulation system and liver such as LysoPC and PC. RNA-Seq and RT-PCR verification revealed that a high amount of quinoa more effectively upregulated genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2] and downregulated genes related to the immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll-like receptor), Tlr10, Tlr11, Tlr12].ConclusionQuinoa effectively prevented NAFLD by controlling body weight, mitigating oxidative stress, and regulating the lipid metabolic profile and the expression of genes related to lipid metabolism and the immune response.

Project description:Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant ?-lipoic acid (?-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (?-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-? (TNF-?) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with ?-LA. Plasma and liver tissue MDA and hepatic TNF-? levels were significantly higher in the HFD group when compared with the control group and significantly lower in the ?-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with ?-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after ?-LA treatment. In conclusion, ?-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-? and reducing oxidative stress. ?-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

Dataset Information

Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.

Publications

Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets