Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 95, Issue -, Pages 65-73Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2016.03.001
Keywords
8-iso-PGF(2 alpha)/PGF(2 alpha) ratio; F2-isoprostanes; Oxidative stress; Inflammation; Biomarkers; Lipid peroxidation
Funding
- Intramural Research Program, National Institutes of Health, National Institute of Environmental Health Sciences
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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 F-2 alpha (8-iso-PGF(2 alpha)), which has been measured in over a thousand human and animal studies. 8-iso-PGF(2 alpha) generation has been exclusively attributed to nonenzymatic chemical lipid peroxidation (CLP). However, 8-iso-PGF(2 alpha) can also be produced enzymatically by prostaglandin-endoperoxide synthases (PGHS) in vivo. When failing to account for PGHS-dependent generation, 8-iso-PGF(2 alpha) cannot be interpreted as a selective biomarker of oxidative stress. We investigated the formation of 8-iso-PGF(2 alpha) in rats exposed to carbon tetrachloride (CCl4) or lipopolysaccharide (LPS) using the 8-iso-PGF(2 alpha)/PGF(2 alpha) ratio to quantitatively determine the source(s) of 8-iso-PGF(2 alpha). Upon exposure to a 120 mg/kg dose of CCl4, the contribution of CLP accounted for only 55.6 +/- 19.4% of measured 8-iso-PGF(2 alpha), whereas in the 1200 mg/kg dose, CLP was the predominant source of 8-iso-PGF(2 alpha) (86.6 +/- 8.0% of total). In contrast to CCl4, exposure to 0.5 mg/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-PGF(2 alpha) 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-PGF(2 alpha)/PGF(2 alpha) ratio accurately determines the source of 8-iso-PGF(2 alpha) and provides an absolute measure of oxidative stress in vivo. (C) 2016 Published by Elsevier Inc.
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