ReviewArchives of toxicology2022
Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose.
Review in Archives of toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 105 citations in OpenAlex.
- Article
- Article
- L-Menthol Attenuates Acetaminophen-Induced Acute Liver Injury Associated with Reduced Oxidative Stress and Ferroptosis-Related Changes.Current issues in molecular biology · 2026Article
- PLGA nanoparticles encapsulating fibroblast growth factor 21 alleviate acetaminophen-induced acute liver injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Imaging bioactive lipid isomers in acetaminophen-induced liver injury using nano-DESI tandem MS.Journal of lipid research · 2026Article
- Probable neuropsychiatric toxicity induced by dihydrocodeine in a peritoneal dialysis patient: a case report and literature review.BMC nephrology · 2026Review
- 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
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Selenium Nanoparticles-Encapsulated Exosomes That Mitigate Acute Liver Injury via an Oral Carboxymethyl Chitosan/Oxidized Dextran Hydrogel.ACS applied materials & interfaces · 2025Article
- Radix Rehmanniae Praeparata Extract Enhances Liver Regeneration Through AMPK-Driven Metabolic Reprogramming.Nutrients · 2025Article
- Electrochemical Point-of-Care Test for Assessing Serum Paracetamol Concentration: Comparison With Traditional Methods and Detection of Concomitant Drugs.Basic & clinical pharmacology & toxicology · 2025Article
- Article
- Can Acetaminophen be Used as a Chemotherapeutic Agent in the Kidney?Journal of biochemical and molecular toxicology · 2025Article
- Trends in Fomepizole Use for Acetaminophen Poisoning in the United States; 2013-2024.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025Article
- Investigation of augmentin-induced hepatobiliary damage and its modulation by N-acetylcysteine in male rats.Open veterinary journal · 2025Article
- Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi TargetingCurrent issues in molecular biology · 2025Article
- Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).Molecular medicine reports · 2025Review
- Dihydromyricetin Alleviated Acetaminophen-Induced Acute Kidney Injury via Nrf2-Dependent Anti-Oxidative and Anti-Inflammatory Effects.International journal of molecular sciences · 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
- Natural Polyphenol-Mediated Inhibition of Ferroptosis Alleviates Oxidative Damage and Inflammation in Acute Liver Injury.Biomaterials research · 2025Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose can cause hepatotoxicity and even liver failure. N-acetylcysteine (NAC) is still the only FDA-approved antidote against APAP overdose 40 years after its introduction. The standard oral or intravenous dosing regimen of NAC is highly effective for patients with moderate overdoses who present within 8 h of APAP ingestion. However, for late-presenting patients or after ingestion of very large overdoses, the efficacy of NAC is diminished. Thus, additional antidotes with an extended therapeutic window may be needed for these patients. Fomepizole (4-methylpyrazole), a clinically approved antidote against methanol and ethylene glycol poisoning, recently emerged as a promising candidate. In animal studies, fomepizole effectively prevented APAP-induced liver injury by inhibiting Cyp2E1 when treated early, and by inhibiting c-jun N-terminal kinase (JNK) and oxidant stress when treated after the metabolism phase. In addition, fomepizole treatment, unlike NAC, prevented APAP-induced kidney damage and promoted hepatic regeneration in mice. These mechanisms of protection (inhibition of Cyp2E1 and JNK) and an extended efficacy compared to NAC could be verified in primary human hepatocytes. Furthermore, the formation of oxidative metabolites was eliminated in healthy volunteers using the established treatment protocol for fomepizole in toxic alcohol and ethylene glycol poisoning. These mechanistic findings, together with the excellent safety profile after methanol and ethylene glycol poisoning and after an APAP overdose, suggest that fomepizole may be a promising antidote against APAP overdose that could be useful as adjunct treatment to NAC. Clinical trials to support this hypothesis are warranted.
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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.