Modulation of Oxidant Stress In Vivo in Chronic Cigarette Smokers

<jats:p><jats:italic>Background</jats:italic>Free radical–induced oxidative damage is thought to be involved in the pathogenesis of diseases associated with cigarette smoking. We examined the production of 8-<jats:italic>epi-</jats:italic>prostaglandin (PG) F<jats:sub>2</jats:sub><jats:sub>α</jats:sub>, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers.</jats:p><jats:p><jats:italic>Methods and Results</jats:italic>We performed the following studies: (1) a cross-sectional comparison of smokers and control subjects, (2) an examination of the dose-response relationship, (3) an exploration of the effect of smoking cessation (3 weeks) and nicotine patch supplementation, (4) the effect of aspirin consumption, and (5) the effects of 5 days’ dosing with vitamin E (100 and 800 U), vitamin C (2 g), and their combination. 8-<jats:italic>epi</jats:italic>-PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>excretion (in pmol/mmol, mean±SEM) was 176.5±30.6 in heavy smokers, 92.7±4.8 (<jats:italic>P</jats:italic><.05) in moderate smokers, and 54.1±2.7 (<jats:italic>P</jats:italic><.005) in nonsmokers. Urinary levels fell from 145.5±24.9 to 114.6±27.1 (week 2,<jats:italic>P</jats:italic><.05) and 112.6±24.9 (week 3,<jats:italic>P</jats:italic><.05) on cessation of smoking. Aspirin treatment failed to suppress urinary levels of 8-<jats:italic>epi-</jats:italic>PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>despite a significant reduction in urinary 11-dehydro-TxB<jats:sub>2</jats:sub>production and suppression of 8-<jats:italic>epi-</jats:italic>PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>and TxB<jats:sub>2</jats:sub>in serum. Vitamin C (pre, 194.6±40.9; post, 137.2±34.1;<jats:italic>P</jats:italic><.05) and a combination of vitamin C and E (pre, 171.0±39.8; post, 133.5±29.6;<jats:italic>P</jats:italic><.05) suppressed urinary 8-<jats:italic>epi-</jats:italic>PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>, whereas vitamin E alone had no effect.</jats:p><jats:p><jats:italic>Conclusions</jats:italic>Urinary 8-<jats:italic>epi-</jats:italic>PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>may represent a noninvasive, quantitative index of oxidant stress in vivo. Elevated levels of 8-<jats:italic>epi-</jats:italic>PGF<jats:sub>2</jats:sub><jats:sub>α</jats:sub>in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy.</jats:p>