Elevated plasma 8-iso-prostaglandin F2α levels in human smokers originate primarily from enzymatic instead of non-enzymatic lipid peroxidation
It is widely accepted that free radicals in tobacco smoke lead to oxidative stress and generate the popular lipid peroxidation biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α). However, 8-iso-PGF2α can simultaneously be produced in vivo by the prostaglandin-endoperoxide synthases (PGHS) induced by inflammation. This inflammation-dependent mechanism has never been considered as a source of elevated 8-iso-PGF2α in tobacco smokers.
The goal of this study is to quantify the distribution of chemical- and PGHS-dependent 8-iso-PGF2α formation in the plasma of tobacco smokers and non-smokers. The influences of gender and hormonal contraceptive use were accounted for. The distribution was determined by measuring the 8-iso-PGF2α/prostaglandin F2α (PGF2α) ratio.
When comparing smokers (n = 28) against non-smokers (n = 30), there was a statistically significant increase in the 8-iso-PGF2α concentration. The source of this increased 8-iso-PGF2α was primarily from PGHS. When stratifying for gender, the increase in 8-iso-PGF2α in male smokers (n = 9) was primarily from PGHS. Interestingly, female smokers on hormonal contraceptives had increased 8-iso-PGF2α in both pathways, whereas those not on hormonal contraceptives did not have increased 8-iso-PGF2α.
In conclusion, increased plasma 8-iso-PGF2α in tobacco smokers has complex origins, with PGHS-dependent formation as the primary source. Accounting for both pathways provides a definitive measurement of both oxidative stress and inflammation.