ArticleCell death & disease2020
Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
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Who cites it
180 citing papers in PubMed, 330 citations in OpenAlex.
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- Spatiotemporally Resolved Protein Tagging for Dynamic and Tissue-Specific Secretome Profiling In Vivo.Angewandte Chemie (International ed. in English) · 2026Article
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- L-Menthol Attenuates Acetaminophen-Induced Acute Liver Injury Associated with Reduced Oxidative Stress and Ferroptosis-Related Changes.Current issues in molecular biology · 2026Article
- Cell death-induced release of the pro-aging protein acyl CoA binding protein (ACBP) into the circulation.Cell death and differentiation · 2026Article
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
- Syringaresinol alleviates acetaminophen-induced hepatocyte ferroptosis through the Nrf2/HO-1 pathway by targeting Caveolin-1.Chinese medicine · 2026Article
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Hepatic supersulfides attenuate acetaminophen-induced liver injury via enhanced detoxification and anti-inflammatory mechanisms.Redox biology · 2026Article
- Hepatokine ORM2 suppresses pathological ferritinophagy to prevent acute tissue injury.Cell death & disease · 2026Article
- MALAT1 promotes acetaminophen-induced hepatocyte pyroptosis by stabilizing Rac1 through its interaction with MTDH and the hepatoprotective role of muniziqi saifula.Molecular and cellular biochemistry · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Vitamin K1 attenuates acetaminophen-induced ferroptotic hepatic damage in mice via targeting keap1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Exploring the correlation between ferroptosis-associated biomarkers and MRI-derived parameters in liver fibrosis associated with metabolic dysfunction-associated steatotic liver disease.Clinical and experimental medicine · 2026Article
- Article
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Cysteine Restriction Induces Ferroptosis Depending on theGastro hep advances · 2026Article
- Modulation of Oxidative and ER Stress Pathways by the ADAM17 Inhibitor GW280264X in LPS-Induced Acute Liver Injury.Life (Basel, Switzerland) · 2025Article
- Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury.World journal of gastroenterology · 2025Review
120 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in APAP-induced hepatotoxicity, the underlying mechanism remains unclear. Ferroptosis is a newly discovered type of cell death that is caused by a loss of cellular redox homeostasis. As glutathione (GSH) depletion triggers APAP-induced hepatotoxicity, we investigated the role of ferroptosis in a murine model of APAP-induced acute liver failure. APAP-induced hepatotoxicity (evaluated in terms of ALT, AST, and the histopathological score), lipid peroxidation (4-HNE and MDA), and upregulation of the ferroptosis maker PTGS2 mRNA were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1). Fer-1 treatment also completely prevented mortality induced by high-dose APAP. Similarly, APAP-induced hepatotoxicity and lipid peroxidation were prevented by the iron chelator deferoxamine. Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation. APAP-induced hepatotoxicity was also prevented by genetic inhibition of acyl-CoA synthetase long-chain family member 4 or α-tocopherol supplementation. We found that ferroptosis is responsible for APAP-induced hepatocyte cell death. Our findings provide new insights into the mechanism of APAP-induced hepatotoxicity and suggest that ferroptosis is a potential therapeutic target for APAP-induced acute liver failure.
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