Evidence map›Paper›PMID 26964509›Full record

ArticleFree radical biology & medicine2016

Reinterpreting the best biomarker of oxidative stress: The 8-iso-prostaglandin F2α/prostaglandin F2α ratio shows complex origins of lipid peroxidation biomarkers in animal models.

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

Abstract read
In one paragraph

Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
6.5field-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

47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Circulating GPER-1, 8-Iso-Prostaglandin FJournal of clinical medicine · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Rapid Lipid Mediator Profiling by Convergence Chromatography-MS/MS.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Effect of SophorOxDiabetes, metabolic syndrome and obesity : targets and therapy · 2024
    Article
  20. Article
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

7 authors at 2 institutions in 1 country.

Thomas J Van't ErveImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA. Electronic address: thomas.vanterve@nih.gov.
Fred B LihEpigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
Casey JelsemaDepartment of Statistics, West Virginia University, Morgantown, WV 26505, USA.
Leesa J DeterdingEpigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
Thomas E ElingEmeritus, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
Ronald P MasonImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
Maria B KadiiskaImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709 NC, USA.
National Institute of Environmental Health Sciences · USWest Virginia University · US

Funding

Biomarkers Of Oxidative Stress StudyZIAES048012 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 2009 to 2018
$3.0M
Biomarkers Of Oxidative Stress StudyZ01ES048012 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 1999 to 2008
$515k
Intramural NIH HHS Z01 ES048012
6 · The paper itself

Abstract

Oxidative stress is elevated in numerous environmental exposures and diseases. Millions of dollars have been spent to try to ameliorate this damaging process using anti-oxidant therapies. Currently, the best accepted biomarker of oxidative stress is the lipid oxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α), which has been measured in over a thousand human and animal studies. 8-iso-PGF2α generation has been exclusively attributed to nonenzymatic chemical lipid peroxidation (CLP). However, 8-iso-PGF2α can also be produced enzymatically by prostaglandin-endoperoxide synthases (PGHS) in vivo. When failing to account for PGHS-dependent generation, 8-iso-PGF2α cannot be interpreted as a selective biomarker of oxidative stress. We investigated the formation of 8-iso-PGF2α in rats exposed to carbon tetrachloride (CCl4) or lipopolysaccharide (LPS) using the 8-iso-PGF2α/PGF2α ratio to quantitatively determine the source(s) of 8-iso-PGF2α. Upon exposure to a 120mg/kg dose of CCl4, the contribution of CLP accounted for only 55.6±19.4% of measured 8-iso-PGF2α, whereas in the 1200mg/kg dose, CLP was the predominant source of 8-iso-PGF2α (86.6±8.0% of total). In contrast to CCl4, exposure to 0.5mg/kg LPS was characterized by a significant increase in both the contribution of PGHS (59.5±7.0) and CLP (40.5±14.0%). In conclusion, significant generation of 8-iso-PGF2α occurs through enzymatic as well as chemical lipid peroxidation. The distribution of the contribution is dependent on the exposure agent as well as the dose. The 8-iso-PGF2α/PGF2α ratio accurately determines the source of 8-iso-PGF2α and provides an absolute measure of oxidative stress in vivo.

Indexed as

AnimalsAntioxidantsBiomarkersCarbon TetrachlorideDinoprostHumansLipid PeroxidationLipopolysaccharidesMaleOxidative StressProstaglandin-Endoperoxide SynthasesRats8-epi-prostaglandin F2alphaAntioxidantsBiomarkersCarbon TetrachlorideDinoprostLipopolysaccharidesProstaglandin-Endoperoxide Synthases8-iso-PGF(2α)/PGF(2α) ratioBiomarkersF(2)-isoprostanesInflammationLipid peroxidationOxidative stress

Identifiers

PMID26964509
PMCPMC6626672
OpenAlexW2296290133

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Registered trials

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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.