Modulation of oxidant stress in vivo in chronic cigarette smokers
Reilly, M.; Delanty, N.; Lawson, J.A.; FitzGerald, G.A.
Circulation 94(1): 19-25
1996
ISSN/ISBN: 0009-7322 PMID: 8964113 Document Number: 467211
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-2alpha, 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-2alpha excretion (in pmol/mmol, mean+-SEM) was 176.5+-30.6 in heavy smokers, 92.7+-4.8 (P lt .05) in moderate smokers, and 54.1+-2.7 (P lt .005) in nonsmokers. Urinary levels fell from 145.5+-24.9 to 114.6+-27.1 (week 2, P lt .05) and 112.6+-24.9 (week 3, P lt .05) on cessation of smoking. Aspirin treatment failed to suppress urinary levels of 8-epi-PGF-2alpha despite a significant reduction in urinary 11-dehydro-TxB-2 production and suppression of 8-epi-PGF-2alpha and TxB-2 in serum. Vitamin C (pre, 194.6+-40.9; post, 137.2+-34.1; P lt .05) and a combination of vitamin C and E (pre, 171.0-39.8; post, 133.5+-29.6; P lt .05) suppressed urinary 8-epi-PGF-2alpha, whereas vitamin E alone had no effect. Conclusions: Urinary 8-epi-PGF-2alpha may represent a noninvasive, quantitative index of oxidant stress in vivo. Elevated levels of 8-epi-PGF-2alpha in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy.