Evidence map›Paper›PMID 29920288›Full record

ReviewFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2018

The role of apoptosis in acetaminophen hepatotoxicity.

Hartmut Jaeschke, Luqi Duan, Jephte Y Akakpo, Anwar Farhood, Anup Ramachandran

Abstract readReview
In one paragraph

Review in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
15.4field-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

65 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Comparative assessment ofFrontiers in nutrition · 2026
    Article
  6. Article
  7. The potential of curcumin in mitigating acetaminophen-induced liver damage.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Iranian journal of basic medical sciences · 2024
    Article
  19. Article
  20. Article

5 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

5 authors at 2 institutions in 1 country.

Hartmut JaeschkeDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA. Electronic address: hjaeschke@kumc.edu.
Luqi DuanDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Jephte Y AkakpoDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Anwar FarhoodDepartment of Pathology, George Washington School of Medicine and Health Sciences, Washington, DC, 200037, USA.
Anup RamachandranDepartment of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
University of Kansas Medical Center · USGeorge Washington University · US

Funding

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 JAESCHKE, HARTMUT W. · 2016 to 2020
$5.5M
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 free radical production, biogenesis and their effect on liver regeneration after Acetaminophen (APAP) overdose.F31DK120194 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI AKAKPO, JEPHTE Y. · 2018 to 2020
$98k
NIDDK NIH HHS F31 DK120194NIDDK NIH HHS R01 DK102142NIGMS NIH HHS P20 GM103549NIGMS NIH HHS P30 GM118247
6 · The paper itself

Abstract

Although necrosis is recognized as the main mode of cell death induced by acetaminophen (APAP) overdose in animals and humans, more recently an increasing number of publications, especially in the herbal medicine and dietary supplement field, claim an important contribution of apoptotic cell death in the pathophysiology. However, most of these conclusions are based on parameters that are not specific for apoptosis. Therefore, the objective of this review was to re-visit the key signaling events of receptor-mediated apoptosis and APAP-induced programmed necrosis and critically analyze the parameters that are being used as evidence for apoptotic cell death. Both qualitative and quantitative comparisons of parameters such as Bax, Bcl-2, caspase processing and DNA fragmentation in both modes of cell death clearly show fundamental differences between apoptosis and cell death induced by APAP. These observations together with the lack of efficacy of pan-caspase inhibitors in the APAP model strongly supports the conclusion that APAP hepatotoxicity is dominated by necrosis or programmed necrosis and does not involve relevant apoptosis. In order not to create a new controversy, it is important to understand how to use these "apoptosis" parameters and properly interpret the data. These issues are discussed in this review.

Indexed as

AcetaminophenAnimalsApoptosisbcl-2-Associated X ProteinCaspasesChemical and Drug Induced Liver InjuryDNA FragmentationEnzyme ActivationHumansMitochondria, LiverAcetaminophenbcl-2-Associated X ProteinCaspasesAcetaminophenApoptosisCaspase activationDNA fragmentationDrug hepatotoxicityProgrammed necrosis

Identifiers

PMID29920288
PMCPMC6087673
OpenAlexW2808993218

What OpenQuestion holds

Textmetadata
LicenceTDM
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.