Modulation of Oxidant Stress In Vivo in Chronic Cigarette Smokers

Abstract

Background 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-epi-prostaglandin (PG) F 2α, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers. Methods and Results 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-epi-PGF 2α excretion (in pmol/mmol, mean±SEM) was 176.5±30.6 in heavy smokers, 92.7±4.8 (P<.05) in moderate smokers, and 54.1±2.7 (P<.005) in nonsmokers. Urinary levels fell from 145.5±24.9 to 114.6±27.1 (week 2,P<.05) and 112.6±24.9 (week 3,P<.05) on cessation of smoking. Aspirin treatment failed to suppress urinary levels of 8-epi-PGF 2α despite a significant reduction in urinary 11-dehydro-TxB 2 production and suppression of 8-epi-PGF 2α and TxB 2 in serum. Vitamin C (pre, 194.6±40.9; post, 137.2±34.1;P<.05) and a combination of vitamin C and E (pre, 171.0±39.8; post, 133.5±29.6;P<.05) suppressed urinary 8-epi-PGF 2α, whereas vitamin E alone had no effect. Conclusions Urinary 8-epi-PGF 2α may represent a noninvasive, quantitative index of oxidant stress in vivo. Elevated levels of 8-epi-PGF 2α in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy.