ArticleArchives of toxicology2021
Delayed administration of N-acetylcysteine blunts recovery after an acetaminophen overdose unlike 4-methylpyrazole.
Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- MSCs overexpressing FGF21 alleviate acetaminophen-induced acute liver injury by eliciting macrophage-mediated phagocytosis.Hepatology communications · 2026Article
- Annexin A5 Maintains Mitochondrial Integrity by Inhibiting mPTP Opening to Protect Against Acetaminophen-Induced Acute Liver Injury.International journal of molecular sciences · 2026Article
- Polygonatum odoratum extract ameliorates acetaminophen-induced acute liver injury by modulating the gut-liver axis and remodeling microbial and ceramide metabolism to suppress hepatic ferroptosis: insights from multi-omics.Frontiers in pharmacology · 2026Article
- Protective effects ofFrontiers in toxicology · 2026Article
- Are New Approach Methodologies (NAMs) the Holy Grail of toxicology?Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Lagerstroemia Speciosa (L.) Pers mitigates acetaminophen-induced acute liver toxicity in rats through modulations of oxidative stress, inflammation, apoptosis and the NF-κB/TNF-α/iNOS, Nrf2/HO-1, signaling pathways.Journal of molecular histology · 2025Article
- The potential of curcumin in mitigating acetaminophen-induced liver damage.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).Molecular medicine reports · 2025Review
- Magnesium isoglycyrrhizinate prevented the liver injury of acetaminophen by promoting mitochondrial biogenesis.Toxicology research · 2025Article
- Small Extracellular Vesicles Engineered Using Click Chemistry to Express Chimeric Antigen Receptors Show Enhanced Efficacy in Acute Liver Failure.Journal of extracellular vesicles · 2025Article
- Kummerowia striata extract protects paracetamol-induced liver injury by modulating the S1P/Nrf2/Keap1 pathway.PloS one · 2025Article
- Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure.Biochemical pharmacology · 2024Review
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice.Archives of toxicology · 2024Article
- Gasdermin-E-Dependent Non-Canonical Pyroptosis Promotes Drug-Induced Liver Failure by Promoting CPS1 deISGylation and Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Spatial analysis of renal acetaminophen metabolism and its modulation by 4-methylpyrazole with DESI mass spectrometry imaging.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- Article
- Narirutin activates TFEB (transcription factor EB) to protect against Acetaminophen-induced liver injury by targeting PPP3/calcineurin.Autophagy · 2023Article
- Differentiated modulation of signaling molecules AMPK and SIRT1 in experimentally drug-induced hepatocyte injury.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
N-acetylcysteine (NAC) is the only clinically approved antidote against acetaminophen (APAP) hepatotoxicity. Despite its efficacy in patients treated early after APAP overdose, NAC has been implicated in impairing liver recovery in mice. More recently, 4-methylpyrazole (4MP, Fomepizole) emerged as a potential antidote in the mouse APAP hepatotoxicity model. The objective of this manuscript was to verify the detrimental effect of NAC and its potential mechanism and assess whether 4MP has the same liability. C57BL/6J mice were treated with 300 mg/kg APAP; 9 h after APAP and every 12 h after that, the animals received either 100 mg/kg NAC or 184.5 mg/kg 4MP. At 24 or 48 h after APAP, parameters of liver injury, mitochondrial biogenesis and cell proliferation were evaluated. Delayed NAC treatment had no effect on APAP-induced liver injury at 24 h but reduced the decline of plasma ALT activities and prevented the shrinkage of the areas of necrosis at 48 h. This effect correlated with down-regulation of key activators of mitochondrial biogenesis (AMPK, PGC-1α, Nrf1/2, TFAM) and reduced expression of Tom 20 (mitochondrial mass) and PCNA (cell proliferation). In contrast, 4MP attenuated liver injury at 24 h and promoted recovery at 48 h, which correlated with enhanced mitochondrial biogenesis and hepatocyte proliferation. In human hepatocytes, 4MP demonstrated higher efficacy in preventing cell death compared to NAC when treated at 18 h after APAP. Thus, due to the wider treatment window and lack of detrimental effects on recovery, it appears that at least in preclinical models, 4MP is superior to NAC as an antidote against APAP overdose.
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Registered trials
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