Modulation of oxidant stress in vivo in chronic cigarette smokers.
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) F2 alpha, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers.


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-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.


CONCLUSIONS
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.
Reilly
M
M
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA.
Delanty
N
N
Lawson
J A
JA
FitzGerald
G A
GA
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes; D006801:Humans; D008875:Middle Aged; D009538:Nicotine / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D012907:Smoking; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D028441:F2-Isoprostanes; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D009538:Nicotine; D015237:Dinoprost; D001205:Ascorbic Acid; D001241:Aspirin