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

ABSTRACT: The biomarker 8-iso-prostaglandin F2? (8-iso-PGF2?) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2? 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-PGF2? to prostaglandin F2? (PGF2?) 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-PGF2? in the plasma of rats. In contrast, the 8-iso-PGF2? 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-PGF2? seen in many human diseases. In conclusion, increases in 8-iso-PGF2? do not necessarily reflect increases in oxidative stress; therefore, past studies using 8-iso-PGF2? as a marker of oxidative stress may have been misinterpreted. The 8-iso-PGF2?/PGF2? 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-PGF2?.

SUBMITTER: van 't Erve TJ 

PROVIDER: S-EPMC4441846 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other