title: Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2α)/PGF(2α) ratio distinguishes chemical from enzymatic lipid peroxidation.
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.
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: thomas.vanterve@nih.gov.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: van 't Erve
authors.affiliation: Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Fred B
authors.initials: FB
authors.lastname: Lih
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Kadiiska
authors.affiliation: Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Leesa J
authors.initials: LJ
authors.lastname: Deterding
authors.affiliation: Emeritus, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Eling
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002853:Chromatography, Liquid; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Biomarkers; F(2)-isoprostanes; Inflammation; Lipid peroxidation; Oxidative stress