ReviewGene expression2021
Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?
Review in Gene expression, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Emerging Role of Ferroptosis in Chemotherapy-Associated Hepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives.ACS pharmacology & translational science · 2026Review
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- Varied Effects of Carnosine and an Antioxidant-Enriched Carnosine Supplement in Paracetamol-Induced Hepatotoxicity Model in Mice.Current issues in molecular biology · 2026Article
- Chemical Compositions, Traditional Applications, and Biological Activities ofMolecules (Basel, Switzerland) · 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
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- DIA-based quantitative proteomics explores the mechanism of amelioration of APAP-induced liver injury by anoectochilus roxburghii (Wall.) Lindl.Frontiers in pharmacology · 2025Article
- Ferroptosis and Intrinsic Drug-induced Liver Injury by Acetaminophen and Other Drugs: A Critical Evaluation and Historical Perspective.Journal of clinical and translational hepatology · 2024Review
- [Total flavonoids ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis.Cell death & disease · 2024Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Effect of the long-term use of a NOAEL dose of acetaminophen (paracetamol) on hepatic, renal, and neural tissues of aged albino rats.Open veterinary journal · 2024Article
- Genipin protects against acute liver injury by abrogating ferroptosis via modification of GPX4 and ALOX15-launched lipid peroxidation in mice.Apoptosis : an international journal on programmed cell death · 2023Article
- Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.Livers · 2023Article
- GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure.International journal of medical sciences · 2023Article
- Acetaminophen-induced liver injury: Molecular mechanism and treatments from natural products.Frontiers in pharmacology · 2023Review
- Article
- The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice.Toxicology and applied pharmacology · 2022Article
- Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.Cell biology and toxicology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Acetaminophen (APAP) hepatotoxicity is the most frequent cause of acute liver failure in the US. The mechanisms of APAP-induced liver injury have been under extensive investigations for decades, and many key events of this necrotic cell death are known today. Initially, two opposing hypotheses for cell death were proposed: reactive metabolite and protein adduct formation versus reactive oxygen and lipid peroxidation (LPO). In the end, both mechanisms were reconciled, and it is now generally accepted that the toxicity starts with formation of reactive metabolites that, after glutathione depletion, bind to cellular proteins, especially on mitochondria. This results in a mitochondrial oxidant stress, which requires amplification through a mitogen-activated protein kinase cascade, leading ultimately to enough reactive oxygen and peroxynitrite formation to trigger the mitochondrial membrane permeability transition and cell death. However, the earlier rejected LPO hypothesis seems to make a comeback recently under a different name: ferroptosis. Therefore, the objective of this review was to critically evaluate the available information about intracellular signaling mechanisms of APAP-induced cell death and those of ferroptosis. Under pathophysiologically relevant conditions, there is no evidence for quantitatively enough LPO to cause cell death, and thus APAP hepatotoxicity is not caused by ferroptosis. However, the role of mitochondria-localized minor LPO remains to be further investigated.
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What OpenQuestion holds
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.