Modulation of oxidant stress in vivo in chronic cigarette smokers

• Published in: Circulation (New York, N.Y.) Vol. 94; no. 1; pp. 19 - 25
• Main Authors: REILLY, M, DELANTY, N, LAWSON, J. A, FITZGERALD, G. A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-07-1996
• Subjects: Administration, Cutaneous; Adolescent; Adult; Antioxidants - therapeutic use; Ascorbic Acid - therapeutic use; Aspirin - therapeutic use; Biological and medical sciences; Cross-Sectional Studies; Dinoprost - analogs & derivatives; Dinoprost - urine; Dose-Response Relationship, Drug; F2-Isoprostanes; Humans; Medical sciences; Middle Aged; Nicotine - therapeutic use; Oxidative Stress - drug effects; Smoking; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - metabolism; Tobacco, tobacco smoking; Toxicology; Vitamin E - therapeutic use; Human; Toxicology; Chronic; Prostaglandin; Tobacco smoking; Exploration; Free radical
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.94.1.19

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) F2 alpha, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers.
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-PGF2 alpha 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-PGF2 alpha despite a significant reduction in urinary 11-dehydro-TxB2 production and suppression of 8-epi-PGF2 alpha and TxB2 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-PGF2 alpha, whereas vitamin E alone had no effect.
Urinary 8-epi-PGF2 alpha may represent a noninvasive, quantitative index of oxidant stress in vivo. Elevated levels of 8-epi-PGF2 alpha in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy.