Evidence map›Paper›PMID 25772010›Full record

ArticleFree radical biology & medicine2015

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2α)/PGF(2α) ratio distinguishes chemical from enzymatic lipid peroxidation.

Thomas J van 't Erve, Fred B Lih, Maria B Kadiiska, Leesa J Deterding, Thomas E Eling, Ronald P Mason

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In one paragraph

Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 4 pooled it
6.4field-weighted citation impact, top 3% 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

75 citing papers in PubMed, 4 syntheses or guidelines pooled it, 120 citations in OpenAlex.

  1. Pooled it
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  11. Elevated Amniotic Fluid 8-Iso-Prostaglandin FAntioxidants (Basel, Switzerland) · 2026
    Article
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  14. Camphorquinone-induced phospholipase AJournal of dental sciences · 2026
    Article
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15 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

6 authors at 1 institution in 1 country.

Thomas J van 't ErveImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: thomas.vanterve@nih.gov.
Fred B LihEpigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Maria B KadiiskaImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Leesa J DeterdingEpigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Thomas E ElingEmeritus, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Ronald P MasonImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
National Institute of Environmental Health Sciences · US

Funding

Quantitative ProteomicsZIAES103005 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DETERDING, LEESA · 2011 to 2017
$5.6M
Biomarkers Of Oxidative Stress StudyZIAES048012 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 2009 to 2018
$3.0M
Intramural NIH HHS Z99 ES999999
6 · The paper itself

Abstract

The biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2α via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF2α to prostaglandin F2α (PGF2α) is established as a quantitative measure to distinguish enzymatic from chemical lipid peroxidation in vitro, in animal models, and in humans. Using this method, we find that chemical lipid peroxidation contributes only 3% to the total 8-iso-PGF2α in the plasma of rats. In contrast, the 8-iso-PGF2α levels in plasma of human males are generated >99% by chemical lipid peroxidation. This establishes the potential for an alternate pathway of biomarker synthesis, and draws into question the source of increases in 8-iso-PGF2α seen in many human diseases. In conclusion, increases in 8-iso-PGF2α do not necessarily reflect increases in oxidative stress; therefore, past studies using 8-iso-PGF2α as a marker of oxidative stress may have been misinterpreted. The 8-iso-PGF2α/PGF2α ratio can be used to distinguish biomarker synthesis pathways and thus confirm the potential change in oxidative stress in the myriad of disease and chemical exposures known to induce 8-iso-PGF2α.

Indexed as

Lipid PeroxidationOxidative StressAdultAnimalsBiomarkersChromatography, LiquidDinoprostEnzyme InhibitorsHumansInflammationMaleProstaglandin-Endoperoxide SynthasesRatsRats, Inbred F344Tandem Mass Spectrometry8-epi-prostaglandin F2alphaBiomarkersDinoprostEnzyme InhibitorsProstaglandin-Endoperoxide SynthasesBiomarkersF(2)-isoprostanesInflammationLipid peroxidationOxidative stress

Identifiers

PMID25772010
PMCPMC4441846
OpenAlexW1981073435

What OpenQuestion holds

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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.