ArticleOncotarget2017
Analysis of molecular mechanisms of 5-fluorouracil-induced steatosis and inflammation in vitro and in mice.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Lipid Accumulation Promotes Tumorigenic Behaviour of Colorectal Cancer Cells.Journal of cellular and molecular medicine · 2026Article
- Targeting mitochondrial dysfunction and apoptosis in 5-fluorouracil-induced cardiotoxicity using kaempferol-mediated selenium nanoparticles.Scientific reports · 2026Article
- Amelioration of 5-Fluorouracil-Induced Hepatorenal Toxicity by Epigallocatechin Gallate-Functionalized Selenium Nanoparticles: A Multi-Targeted Protective Approach.International journal of molecular sciences · 2026Article
- Regulatory Mechanisms and Safety Evaluation of Exogenous Progesterone for Suppression of Rutting Behavior in Male Sika Deer (Animals : an open access journal from MDPI · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Scaffold implantationAnnals of surgical treatment and research · 2025Article
- Anticancer Chemotherapy-Induced Atherosclerotic Cardiovascular Disease: A Comprehensive Review.Life (Basel, Switzerland) · 2025Review
- In Vitro Human Liver Model for Toxicity Assessment with Clinical and Preclinical Instrumentation.Pharmaceutics · 2024Article
- Hepatoprotective effect of Nobiletin against 5-fluorouracil induce hepatotoxicity.Current research in pharmacology and drug discovery · 2024Article
- 5-Fluorouracil-associated severe hypertriglyceridaemia with positive rechallenge.BMJ case reports · 2023Article
- Specifics of Pharmacokinetics and Biodistribution of 5-Fluorouracil Polymeric Complex.Molecules (Basel, Switzerland) · 2023Article
- Metabolism and Anticancer Mechanisms of Selocompounds: Comprehensive Review.Biological trace element research · 2023Review
- A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs.Antioxidants (Basel, Switzerland) · 2023Article
- Clearing Steatosis Prior to Liver Surgery for Colorectal Metastasis: A Narrative Review and Case Illustration.Nutrients · 2022Review
- Article
- Effect of lycopene as an adjuvant therapy with 5-florouracil in human colon cancer.Saudi journal of biological sciences · 2022Article
- BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH.Nature metabolism · 2022Article
- Article
- Detailed Molecular Mechanisms Involved in Drug-Induced Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: An Update.Biomedicines · 2022Review
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-associated steatohepatitis is attracting increasing attention because it heralds an increased risk of morbidity and mortality in patients undergoing surgery because of liver metastases. The aim of this study was to develop in vitro and in vivo models to analyze the pathogenesis of 5-fluorouracil (5-FU)-induced steatohepatitis.Therefore, primary human hepatocytes and HepG2 hepatoma cells were incubated with 5-FU at non-toxic concentrations up to 24 h. Furthermore, hepatic tissue of C57BL/6N mice was analyzed 24 h after application of a single 5-FU dose (200 mg/kg body weight). In vitro, incubation with 5-FU induced a significant increase of hepatocellular triglyceride levels. This was paralleled by an impairment of mitochondrial function and a dose- and time-dependently increased expression of fatty acid acyl-CoA oxidase 1 (ACOX1), which catalyzes the initial step for peroxisomal β-oxidation. The latter is known to generate reactive oxygen species, and consequently, expression of the antioxidant enzyme heme oxygenase 1 (HMOX1) was significantly upregulated in 5-FU-treated cells, indicative for oxidative stress. Furthermore, 5-FU significantly induced c-Jun N-terminal kinase (JNK) activation and the expression of pro-inflammatory genes IL-8 and ICAM-1. Also in vivo, 5-FU significantly induced hepatic ACOX1 and HMOX1 expression as well as JNK-activation, pro-inflammatory gene expression and immune cell infiltration. In summary, we identified molecular mechanisms by which 5-FU induces hepatocellular lipid accumulation and inflammation. Our newly developed models can be used to gain further insight into the pathogenesis of 5-FU-induced steatohepatitis and to develop therapeutic strategies to inhibit its development and progression.
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