ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Amiodarone exposure during modest inflammation induces idiosyncrasy-like liver injury in rats: role of tumor necrosis factor-alpha.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Insights into the Biochemical and Immune Mechanisms in Drug-Induced Liver Injury Pathogenesis.Chemical research in toxicology · 2026Review
- Susceptibility Factor TNF-α Synergizes withJournal of inflammation research · 2025Article
- Ethanolic Extracts of Cupressaceae Species Conifers Provide Rapid Protection against Barium Chloride-Induced Cardiac Arrhythmia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Macrophage malfunction in Triptolide-induced indirect hepatotoxicity.Frontiers in pharmacology · 2022Article
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- The protective potential of alpha lipoic acid on amiodarone-induced pulmonary fibrosis and hepatic injury in rats.Molecular and cellular biochemistry · 2021Article
- Immune-Mediated Drug-Induced Liver Injury: Immunogenetics and Experimental Models.International journal of molecular sciences · 2021Review
- The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury.Acta pharmacologica Sinica · 2021Review
- Article
- Liver Enzyme Elevations inThe American journal of tropical medicine and hygiene · 2020Article
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- A new perspective of triptolide-associated hepatotoxicity: the relevance of NF-Acta pharmaceutica Sinica. B · 2020Article
- Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models.Nature reviews. Drug discovery · 2020Review
- Animal models of drug-induced liver injury.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Trends in reporting drug-associated liver injuries in Taiwan: a focus on amiodarone.International journal of clinical pharmacy · 2018Article
- Model-based identification of TNFα-induced IKKβ-mediated and IκBα-mediated regulation of NFκB signal transduction as a tool to quantify the impact of drug-induced liver injury compounds.NPJ systems biology and applications · 2018Article
- Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity.Frontiers in pharmacology · 2018Article
- "Autoimmune(-Like)" Drug and Herb Induced Liver Injury: New Insights into Molecular Pathogenesis.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Amiodarone [2-butyl-3-(3',5'-diiodo-4'α-diethylaminoethoxybenzoyl)-benzofuran] (AMD), a class III antiarrhythmic drug, is known to cause idiosyncratic hepatotoxic reactions in human patients. One hypothesis for the etiology of idiosyncratic adverse drug reactions is that a concurrent inflammatory stress results in decreased threshold for drug toxicity. To explore this hypothesis in an animal model, male Sprague-Dawley rats were treated with nonhepatotoxic doses of AMD or its vehicle and with saline vehicle or lipopolysaccharide (LPS) to induce low-level inflammation. Elevated alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities as well as increased total bile acid concentrations in serum and midzonal hepatocellular necrosis were observed only in AMD/LPS-cotreated rats. The time interval between AMD and LPS administration was critical: AMD injected 16 h before LPS led to liver injury, whereas AMD injected 2-12 h before LPS failed to cause this response. The increase in ALT activity in AMD/LPS cotreatment showed a clear dose-response relationship with AMD as well as LPS. The metabolism and hepatic accumulation of AMD were not affected by LPS coexposure. Serum concentration of tumor necrosis factor-alpha (TNF) was significantly increased by LPS and was slightly prolonged by AMD. In Hepac1c7 cells, addition of TNF potentiated the cytotoxicity of both AMD and its primary metabolite, mono-N-desethylamiodarone. In vivo inhibition of TNF signaling by etanercept attenuated the AMD/LPS-induced liver injury in rats. In summary, AMD treatment during modest inflammation induced severe hepatotoxicity in rats, and TNF contributed to the induction of liver injury in this animal model of idiosyncratic AMD-induced liver injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.