ReviewToxicological sciences : an official journal of the Society of Toxicology2020
Novel Therapeutic Approaches Against Acetaminophen-induced Liver Injury and Acute Liver Failure.
Review in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review.Drug safety · 2022Pooled it
- Superoxide Dismutase Administration: A Review of Proposed Human Uses.Molecules (Basel, Switzerland) · 2021Pooled it
- Integrated transcriptomic and experimental validation reveal that N‑acetylcysteine ameliorates acute liver failure through multi‑target synergistic regulation of pyroptosis and related signaling networks.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Vitamin A-coupled MSCs- derived extracellular vesicles relieve acute liver injury by targeting hepatic stellate cells to deliver REDD1.Journal of nanobiotechnology · 2026Article
- Varied Effects of Carnosine and an Antioxidant-Enriched Carnosine Supplement in Paracetamol-Induced Hepatotoxicity Model in Mice.Current issues in molecular biology · 2026Article
- Prostaglandin E2 alleviates acetaminophen-induced liver injury through DDIT4-enhanced autophagy regulated by circLima1/miR-486.Scientific reports · 2026Article
- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- Network pharmacology, molecular docking, molecular dynamics simulation, and in vivo experiments elucidate the potential mechanisms of berberine against liver injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Toxicoproteomics of APAP-exposed HepG2 cells identifies candidate translational biomarkers of liver injury and recovery.Frontiers in pharmacology · 2026Article
- Navigating Global Regulatory Divergence in Over-the-counter Drugs: Addressing Emerging Risks and Harmonization Challenges.Current drug research reviews · 2026Review
- Sesamin alleviates drug-induced hepatotoxicity via autophagy enhancement and ferroptosis inhibition.Redox report : communications in free radical research · 2025Article
- Article
- Evaluation of Nutraceutical Potential ofFood science & nutrition · 2025Article
- Exosome-mediated Transfer of lncRNA in Liver Associated Diseases; Uncovered Truths.Cell biochemistry and biophysics · 2025Review
- Nimbolide Targeting SIRT1 Protects Against Acetaminophen-Induced Acute Liver Injury by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.Pharmacology research & perspectives · 2025Article
- Paracetamol: the potential therapeutic pathways defining its clinical use.Inflammopharmacology · 2025Review
- Insights into medication-induced liver injury: Understanding and management strategies.Toxicology reports · 2025Review
- Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.Biomolecules & therapeutics · 2025Article
- Research progress on the molecular mechanisms of Saikosaponin D in various diseases (Review).International journal of molecular medicine · 2025Review
- The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
28 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
Liver injury and acute liver failure caused by acetaminophen (APAP, N-acetyl-p-aminophenol, paracetamol) overdose is a significant clinical problem in most western countries. The only clinically approved antidote is N-acetylcysteine (NAC), which promotes the recovery of hepatic GSH. If administered during the metabolism phase, GSH scavenges the reactive metabolite N-acetyl-p-benzoquinone imine. More recently, it was shown that NAC can also reconstitute mitochondrial GSH levels and scavenge reactive oxygen/peroxynitrite and can support mitochondrial bioenergetics. However, NAC has side effects and may not be efficacious after high overdoses. Repurposing of additional drugs based on their alternate mechanisms of action could be a promising approach. 4-Methylpyrazole (4MP) was shown to be highly effective against APAP toxicity by inhibiting cytochrome P450 enzymes in mice and humans. In addition, 4MP is a potent c-Jun N-terminal kinase inhibitor expanding its therapeutic window. Calmangafodipir (CMFP) is a SOD mimetic, which is well tolerated in patients and has the potential to be effective after severe overdoses. Other drugs approved for humans such as metformin and methylene blue were shown to be protective in mice at high doses or at human therapeutic doses, respectively. Additional protective strategies such as enhancing antioxidant activities, Nrf2-dependent gene induction and autophagy activation by herbal medicine components are being evaluated. However, at this point, their mechanistic insight is limited, and the doses used are high. More rigorous mechanistic studies are needed to advance these herbal compounds. Nevertheless, based on recent studies, 4-methylpyrazole and calmangafodipir have realistic prospects to become complimentary or even alternative antidotes to NAC for APAP overdose.
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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.