ArticlePloS one2014
Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Mechanism-based new approach methodologies for in vitro detection of chemical-induced liver steatosis.Archives of toxicology · 2026Review
- Drugs with glutamate-based mechanisms of action in psychiatry.Pharmacological reports : PR · 2024Review
- Investigating the tamoxifen/high-fat diet synergy: a promising paradigm for nonalcoholic steatohepatitis induction in a rat model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Computational Strategies for Assessing Adverse Outcome Pathways: Hepatic Steatosis as a Case Study.International journal of molecular sciences · 2024Review
- Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and PPARα knockout mouse hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Integrated bioinformatics and interaction analysis to advance chronotherapies for mental disorders.Frontiers in pharmacology · 2024Article
- Predicting Valproate-Induced Liver Injury Using Metabolomic Analysis of Ex Ovo Chick Embryo Allantoic Fluid.Metabolites · 2023Article
- Quantitative chemometric phenotyping of three-dimensional liver organoids by Raman spectral imaging.Cell reports methods · 2023Article
- In Vitro Models for Studying Chronic Drug-Induced Liver Injury.International journal of molecular sciences · 2022Review
- Liraglutide Exerts Protective Effects by Downregulation ofCurrent issues in molecular biology · 2022Article
- Article
- Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods.International journal of molecular sciences · 2022Review
- Detailed Molecular Mechanisms Involved in Drug-Induced Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: An Update.Biomedicines · 2022Review
- Drug-induced Fatty Liver Disease: Pathogenesis and Treatment.Journal of clinical and translational hepatology · 2021Review
- Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity.Cell biology and toxicology · 2021Article
- Reproducibility and robustness of high-throughput S1500+ transcriptomics on primary rat hepatocytes for chemical-induced hepatotoxicity assessment.Current research in toxicology · 2021Article
- Prospects for repurposing CNS drugs for cancer treatment.Oncology reviews · 2019Article
- Article
- Mining Public Toxicogenomic Data Reveals Insights and Challenges in Delineating Liver Steatosis Adverse Outcome Pathways.Frontiers in genetics · 2019Article
- FGF21 Is Associated with Metabolic Effects and Treatment Response in Depressed Bipolar II Disorder Patients Treated with Valproate.The international journal of neuropsychopharmacology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR) signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism.
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