Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF2α/PGF2α, ratio distinguishes chemical from enzymatic lipid peroxidation

The biomarker 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF(2 alpha) 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-PGF(2 alpha) to prostaglandin F-2 alpha (PGF(2 alpha)) 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-PGF(2 alpha) in the plasma of rats. In contrast, the 8-iso-PGF(2 alpha) 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-PGF(2 alpha) seen in many human diseases. In conclusion, increases in 8-iso-PGF(2 alpha) do not necessarily reflect increases in oxidative stress: therefore, past studies using 8-iso-PGF(2 alpha) as a marker of oxidative stress may have been misinterpreted. The 8-isoPGF(2 alpha)/PGF(2 alpha) 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-PGFF(2 alpha). Published by Elsevier Inc.