ArticleReactive oxygen species (Apex, N.C.)2018
Oxidant Stress and Lipid Peroxidation in Acetaminophen Hepatotoxicity.
Article in Reactive oxygen species (Apex, N.C.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The trial behind it
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Who cites it
28 citing papers in PubMed, 67 citations in OpenAlex.
- Casticin Alleviates Acetaminophen-Induced Acute Liver Injury by Modulating the TLR4/MyD88/TRAF6/NF-κB Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The paradoxical protective effect of malnutrition in acetaminophen-induced liver injury.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Hepatoprotective effects of silybin in liver fibrosis.World journal of gastroenterology · 2025Review
- The multiple mechanisms and modes of cell death after acetaminophen overdose.Exploration of digestive diseases · 2025Article
- Delayed treatment with hydro-ethanolic extract ofPharmaceutical science advances · 2024Article
- The protective effect of Thai rice bran on N-acetyl-ρ-aminophen-induced hepatotoxicity in mice.Research in pharmaceutical sciences · 2024Article
- Identifying metabolic adaptations characteristic of cardiotoxicity using paired transcriptomics and metabolomics data integrated with a computational model of heart metabolism.PLoS computational biology · 2024Article
- Hepatocyte-specific deletion of small heterodimer partner protects mice against acetaminophen-induced hepatotoxicity via activation of Nrf2.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Galactosylated hydroxyl-polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning-induced liver failure.Bioengineering & translational medicine · 2023Article
- LP342, a novel histone deacetylase inhibitor, decreases nitro-oxidative stress, mitochondrial dysfunction and hepatic ischaemia/reperfusion injury in mice.RPS pharmacy and pharmacology reports · 2023Article
- GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure.International journal of medical sciences · 2023Article
- Hepatoprotective Effect of Kaempferol: A Review of the Dietary Sources, Bioavailability, Mechanisms of Action, and Safety.Advances in pharmacological and pharmaceutical sciences · 2023Review
- Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice.Journal of natural products · 2022Review
- The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice.Toxicology and applied pharmacology · 2022Article
- Epitranscriptomic Reprogramming Is Required to Prevent Stress and Damage from Acetaminophen.Genes · 2022Article
- Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1.Pharmaceutical biology · 2021Article
- Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls.Acta pharmaceutica Sinica. B · 2021Review
- CD36 deficiency ameliorates drug-induced acute liver injury in mice.Molecular medicine (Cambridge, Mass.) · 2021Article
- Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.Antioxidants (Basel, Switzerland) · 2021Review
- The antioxidant activities of Korean Red Ginseng (Journal of ginseng research · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose is the most frequent cause of liver injury and acute liver failure in many western countries. The mechanism of APAP-induced hepatocyte necrosis has been investigated extensively. The formation of a reactive metabolite and its binding to cellular proteins was initially thought to be responsible for cell death. A competing hypothesis was introduced that questioned the relevance of protein binding and instead suggested that P450-derived oxidant stress and lipid peroxidation causes APAP-induced liver injury. However, work over the last 15 years has reconciled some of these apparent contradictory hypotheses. This review summarizes the present state of knowledge on the role of reactive oxygen species (ROS) in APAP hepatotoxicity. Detailed investigations into the sources and relevance of the oxidant stress have clearly shown the critical role of the electron transport chain of mitochondria as main source of the oxidant stress. Other potential sources of ROS such as cytochrome P450 enzymes or NADPH oxidase on phagocytes are of limited relevance. The mitochondria-derived superoxide and peroxynitrite formation is initiated by the binding of the reactive metabolite to mitochondrial proteins and the amplification by mitogen activated protein kinases. The consequences of this oxidant stress are the opening of the mitochondrial membrane permeability transition pore with cessation of ATP synthesis, nuclear DNA fragmentation and ultimately cell necrosis. Lipid peroxidation is not a relevant mechanism of cell death but can be a marker of ROS formation. These mechanistic insights suggest that targeting mitochondrial oxidant stress is a promising therapeutic option for APAP hepatotoxicity.
Indexed as
Identifiers
29682614PMC5903282W2794938183What 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.