Evidence map›Paper›PMID 27744120›Full record

ReviewRedox biology2016

Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential.

Kuo Du, Anup Ramachandran, Hartmut Jaeschke

Open access · goldAbstract readReview
In one paragraph

Review in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
257citing papers in PubMed, 1 pooled it
58.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

257 citing papers in PubMed, 1 synthesis or guideline pooled it, 537 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Acetaminophen-induced acute liver injury abrogates the cytosine methylation pathway.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2026
    Article
  10. Article
  11. The paradoxical protective effect of malnutrition in acetaminophen-induced liver injury.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Exposure to Acetaminophen (Paracetamol) during Pregnancy and Childhood Cancer: A Population-Based Cohort Study in Taiwan.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
  19. Pharmaceutics · 2026
    Review
  20. Herb-Induced Liver Injury byLife (Basel, Switzerland) · 2026
    Article

197 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Kuo DuDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 1018, Kansas City, Kansas, USA. Electronic address: kdu@kumc.edu.
Anup RamachandranDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 1018, Kansas City, Kansas, USA. Electronic address: aramachandran@kumc.edu.
Hartmut JaeschkeDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 1018, Kansas City, Kansas, USA. Electronic address: hjaeschke@kumc.edu.
University of Kansas Medical Center · US

Funding

THE ROLE OF HUMAN PXR IN ANTI-TUBERCULOSIS DRUG-INDUCED LIVER INJURYP20RR021940 · NCRR · UNIVERSITY OF KANSAS MEDICAL CENTER · PI KRISHNAMURTHY, PARTHA C · 2006 to 2011
$12.1M
Nuclear Receptors in Liver Health and DiseaseP20GM103549 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2012 to 2015
$8.1M
Pilot Grants ProgramP30GM118247 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI WEINMAN, STEVEN A · 2016 to 2020
$5.5M
NEUTROPHIL-INDUCED LIVER INJURY TOXICITYR01AA012916 · NIAAA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2001 to 2012
$2.9M
Autophagy and Drug-Induced Liver InjuryR01DK102142 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI DING, WEN-XING, JAESCHKE, HARTMUT W. · 2014 to 2022
$2.7M
Mitochondrial Dysfunction and Drug HepatotoxicityR01DK070195 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2005 to 2010
$1.8M
NCRR NIH HHS P20 RR021940NIAAA NIH HHS R01 AA012916NIDDK NIH HHS R01 DK070195NIDDK NIH HHS R01 DK102142NIGMS NIH HHS P20 GM103549NIGMS NIH HHS P30 GM118247
6 · The paper itself

Abstract

Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P450-generated reactive oxygen species (ROS) during APAP metabolism, which resulted in massive lipid peroxidation and subsequent liver injury. However, subsequent studies convincingly challenged this assumption and the current paradigm suggests that mitochondria are the main source of ROS, which impair mitochondrial function and are responsible for cell signaling resulting in cell death. Although immune cells can be a source of ROS in other models, no reliable evidence exists to support a role for immune cell-derived ROS in APAP hepatotoxicity. Recent studies suggest that mitochondrial targeted antioxidants can be viable therapeutic agents against hepatotoxicity induced by APAP overdose, and re-purposing existing drugs to target oxidative stress and other concurrent signaling events can be a promising strategy to increase its potential application in patients with APAP overdose.

Indexed as

AcetaminophenAnimalsChemical and Drug Induced Liver InjuryDrug RepositioningLipid PeroxidationMitochondriaOxidative StressReactive Oxygen SpeciesAcetaminophenReactive Oxygen SpeciesAcetaminophen hepatotoxicity, mitochondria, oxidant stressAntioxidantsInnate immunityLipid peroxidationPeroxynitrite

Identifiers

PMID27744120
PMCPMC5065645
OpenAlexW2529405505

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.