ReviewLife sciences2011
Current issues with acetaminophen hepatotoxicity--a clinically relevant model to test the efficacy of natural products.
Review in Life sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
97 citing papers in PubMed, 227 citations in OpenAlex.
- Paracetamol-induced hepatic injury following intentional self-poisoning: a case report and therapeutic considerations.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Varied Effects of Carnosine and an Antioxidant-Enriched Carnosine Supplement in Paracetamol-Induced Hepatotoxicity Model in Mice.Current issues in molecular biology · 2026Article
- Role of the Plasminogen Activation System in Liver Injury and Repair: Knowns and Known Unknowns.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Paracetamol Induces Apoptosis, Reduces Colony Formation, and Increases PTPRO Gene Expression in Human Embryonic Kidney HEK 293 Cells.Journal of biochemical and molecular toxicology · 2025Article
- CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.Acta pharmaceutica Sinica. B · 2025Article
- Associations of maternal blood biomarkers of prenatal APAP exposure with placental gene expression and child attention deficit hyperactivity disorder.Nature. Mental health · 2025Article
- Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.Journal of dietary supplements · 2025Review
- Flaxseed Lignan Alleviates the Paracetamol-Induced Hepatotoxicity Associated with Regulation of Gut Microbiota and Serum Metabolome.Nutrients · 2024Article
- The Relationship between Prohibitin 1 Expression, Hepatotoxicity Induced by Acetaminophen, and Hepatoprotection by S-Adenosylmethionine in AML12 Cells.Journal of microbiology and biotechnology · 2022Article
- Desorption Electrospray Ionization Mass Spectrometry Imaging Allows Spatial Localization of Changes in Acetaminophen Metabolism in the Liver after Intervention with 4-Methylpyrazole.Journal of the American Society for Mass Spectrometry · 2022Article
- Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling.International journal of molecular sciences · 2022Article
- Piperine as Therapeutic Agent in Paracetamol-Induced Hepatotoxicity in Mice.Pharmaceutics · 2022Article
- Gastrodin Alleviates Acetaminophen-Induced Liver Injury in a Mouse Model Through Inhibiting MAPK and Enhancing Nrf2 Pathways.Inflammation · 2022Article
- Chemico-Pharmacological Screening of the Methanol Extract ofMolecules (Basel, Switzerland) · 2022Article
- Hepatorenal Protective Effects of Hydroalcoholic Extract ofJournal of toxicology · 2022Article
- Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models.Cells · 2021Article
- Hepatoprotective Glucosyloxybenzyl 2-Hydroxy-2-isobutylsuccinates fromJournal of natural products · 2021Article
- Protective role of Chlorella vulgaris with Thiamine against Paracetamol induced toxic effects on haematological, biochemical, oxidative stress parameters and histopathological changes in Wistar rats.Scientific reports · 2021Article
- Dibenzazepine combats acute liver injury in rats via amendments of Notch signaling and activation of autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Acetaminophen Test Battery (ATB): A Comprehensive Method to Study Acetaminophen-Induced Acute Liver Injury.Gene expression · 2020Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
There is a significant need to evaluate the therapeutic potential of natural products and other compounds purported to be hepatoprotective. Acetaminophen-induced liver injury, especially in mice, is an attractive and widely used model for this purpose because it is both clinically relevant and experimentally convenient. However, the pathophysiology of liver injury after acetaminophen overdose is complex. This review describes the multiple steps and signaling pathways involved in acetaminophen-mediated cell death. The toxicity is initiated by the formation of a reactive metabolite, which depletes glutathione and binds to cellular proteins, especially in mitochondria. The resulting mitochondrial oxidant stress and peroxynitrite formation, in part through amplification by c-jun-N-terminal kinase activation, leads to mitochondrial DNA damage and opening of the mitochondrial permeability transition pore. Endonucleases from the mitochondrial intermembrane space and lysosomes are responsible for nuclear DNA fragmentation. Despite the oxidant stress, lipid peroxidation is not a relevant mechanism of injury. The mitochondrial dysfunction and nuclear DNA damage ultimately cause oncotic necrotic cell death with release of damage-associated molecular patterns that trigger a sterile inflammatory response. Current evidence supports the hypothesis that innate immune cells do not contribute to injury but are involved in cell debris removal and regeneration. This review discusses the latest mechanistic aspects of acetaminophen hepatotoxicity and demonstrates ways to assess the mechanisms of drug action and design experiments needed to avoid pitfalls and incorrect conclusions. This review should assist investigators in the optimal use of this model to test the efficacy of natural compounds and obtain reliable mechanistic information.
Indexed as
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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.