Reinterpreting the best biomarker of oxidative stress: The 8-iso-prostaglandin F2?/prostaglandin F2? ratio shows complex origins of lipid peroxidation biomarkers in animal models.

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 F2? (8-iso-PGF2?), which has been measured in over a thousand human and animal studies. 8-iso-PGF2? generation has been exclusively attributed to nonenzymatic chemical lipid peroxidation (CLP). However, 8-iso-PGF2? can also be produced enzymatically by prostaglandin-endoperoxide synthases (PGHS) in vivo. When failing to account for PGHS-dependent generation, 8-iso-PGF2? cannot be interpreted as a selective biomarker of oxidative stress. We investigated the formation of 8-iso-PGF2? in rats exposed to carbon tetrachloride (CCl4) or lipopolysaccharide (LPS) using the 8-iso-PGF2?/PGF2? ratio to quantitatively determine the source(s) of 8-iso-PGF2?. Upon exposure to a 120mg/kg dose of CCl4, the contribution of CLP accounted for only 55.6±19.4% of measured 8-iso-PGF2?, whereas in the 1200mg/kg dose, CLP was the predominant source of 8-iso-PGF2? (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-PGF2? 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-PGF2?/PGF2? ratio accurately determines the source of 8-iso-PGF2? and provides an absolute measure of oxidative stress in vivo.

SUBMITTER: Van't Erve TJ 

PROVIDER: S-EPMC6626672 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature