ReviewDrug metabolism and disposition: the biological fate of chemicals2024
Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.
Review in Drug metabolism and disposition: the biological fate of chemicals, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Viburnum opulus protects against acetaminophen-induced splenic injury through coordinated antioxidant and anti-inflammatory responses.Journal of molecular histology · 2026Article
- Mitochondrial quality control in acute liver injury and its therapeutic implications (Review).Molecular medicine reports · 2026Review
- Article
- Molecular Mechanisms of Acute Drug Toxicity in Polypharmacy: Analgesic-Psychotropic Interactions.International journal of molecular sciences · 2026Review
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Malic Enzyme 1 Limits Acetaminophen-Induced Liver Injury by Sustaining Redox and Bioenergetic Homeostasis.Metabolites · 2026Article
- Investigating the Therapeutic Activity of CACS omega · 2026Article
- Hepatic STEAP4 promotes liver regeneration by regulating lysosomal iron homeostasis and membrane integrity in acetaminophen-induced liver injury.Hepatology (Baltimore, Md.) · 2026Article
- Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis.Immunity · 2026Article
- Differential effects on acetaminophen-induced nephrotoxicity and liver injury following modulation of glutathione resynthesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026Article
- Binankadsurin A fromNutrients · 2026Article
- Severe Acute Liver Injury Following Repeated Supratherapeutic Paracetamol Ingestion in a Child: A Case Report from a Resource-Limited Setting.International medical case reports journal · 2026Article
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Sonochemically enhanced activated charcoal with improved oral palatability for efficient in vitro detoxification of acetaminophen.Scientific reports · 2025Article
- Unraveling the Antihyperglycemic Effects of Dipeptyl Peptidase-4 Inhibitors in Rodents: A Multi-Faceted Approach Combining Effects on Glucose Homeostasis, Molecular Docking, and ADMET Profiling.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Sakuranetin Prevents Acetaminophen-Induced Liver Injury via Nrf2-Induced Inhibition of Hepatocyte Ferroptosis.Drug design, development and therapy · 2025Article
- Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure.Biochemical pharmacology · 2024Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Acetaminophen (APAP) is an analgesic and antipyretic drug used worldwide, which is safe at therapeutic doses. However, an overdose can induce liver injury and even liver failure. Mechanistic studies in mice beginning with the seminal papers published by B.B. Brodie's group in the 1970s have resulted in important insight into the pathophysiology. Although the metabolic activation of APAP with generation of a reactive metabolite, glutathione depletion, and protein adduct formation are critical initiating events, more recently, mitochondria have come into focus as an important target and decision point of cell death. This review provides a comprehensive overview of the induction of mitochondrial superoxide and peroxynitrite formation and its propagation through a mitogen-activated protein kinase cascade, the mitochondrial permeability transition pore opening caused by iron-catalyzed protein nitration, and the mitochondria-dependent nuclear DNA fragmentation. In addition, the role of adaptive mechanisms that can modulate the pathophysiology, including autophagy, mitophagy, nuclear erythroid 2 p45-related factor 2 activation, and mitochondrial biogenesis, are discussed. Importantly, it is outlined how the mechanisms elucidated in mice translate to human hepatocytes and APAP overdose patients, and how this mechanistic insight explains the mechanism of action of the clinically approved antidote
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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.