ArticlePloS one2010
Acetaminophen induces apoptosis in rat cortical neurons.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology.Environmental health : a global access science source · 2025Pooled it
- Efficacy and Safety of Paracetamol for Patent Ductus Arteriosus Closure in Preterm Infants: An Updated Systematic Review and Meta-Analysis.Frontiers in pediatrics · 2019Pooled it
- High Doses of N-Acetyl-P-Aminophenol Cause Acute Changes in Electroencephalographic and Electrocardiographic Activities in Wistar Rats.Basic & clinical pharmacology & toxicology · 2026Article
- Could NAPQI Contribute to Paracetamol Analgesia? Redox Modulation of Kv7 Ion Channels.Pharmacology research & perspectives · 2026Review
- Gestational Paracetamol (Acetaminophen) Toxicity Induces Behavioral and Structural Brain Defects in Rats.Current issues in molecular biology · 2026Article
- Acetaminophen exposure in an aging population and neurodegenerative outcomes.European journal of clinical pharmacology · 2026Article
- Repurposing Leucovorin for Mild Traumatic Brain Injury: Evidence from Biochemical and Behavioral Outcomes in Rats.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The possible effect of coenzyme Q10 and captopril on acetaminophen-induced encephalopathy in rats: possible influence on autophagy, antioxidant and NaArchives of medical science : AMS · 2025Article
- Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder.Life (Basel, Switzerland) · 2024Article
- Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden.Scientific reports · 2024Article
- Acetaminophen causes neurodevelopmental injury in susceptible babies and children: no valid rationale for controversy.Clinical and experimental pediatrics · 2024Article
- Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose.International journal of molecular sciences · 2024Article
- Review
- The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits.Children (Basel, Switzerland) · 2023Review
- Article
- Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death.International journal of molecular sciences · 2022Article
- Small molecule inhibitors of α-synuclein oligomers identified by targeting early dopamine-mediated motor impairment in C. elegans.Molecular neurodegeneration · 2021Article
- Paracetamol (Acetaminophen) and the Developing Brain.International journal of molecular sciences · 2021Review
- 2021 ISHEN guidelines on animal models of hepatic encephalopathy.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes.American journal of epidemiology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. METHODOLOGY/PRINCIPAL
findingsWe report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM) that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/kg) that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial-mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/kg) injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. CONCLUSIONS/SIGNIFICANCE: The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment) are present.
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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.