During all aerobic metabolism, free radicals generated by the partial reduction of oxygen are potentially injurious to cells. Highly efficient antioxidant defence systems exist to inhibit oxidative damage to cellular lipids and proteins. Specific enzymes have a crucial role in these antioxidant defences, and their activity may be induced by regulatory mechanisms that respond to oxygen metabolite concentration. 2. To assess whether smoking induces an additional adaptive response, we compared antioxidant defence systems in erythrocytes from smokers and non-smokers and assessed whether a high intake of vitamin E (280 mg/day), a major lipophilic free-radical-scavenging antioxidant, affects the activity of antioxidant enzymes. 3. A total of 100 men, 50 smokers and 50 non-smokers, were allocated to four treatment groups in a 2 x 2 factorial design (smokers versus non-smokers and placebo versus vitamin E). For 10 weeks each subject took one capsule per day of either 280 mg dl-alpha-tocopherol acetate or a visually identical placebo (hydrogenated coconut oil with negligible vitamin E content). 4. Despite increased erythrocyte cytosolic antioxidant enzyme activities in smokers compared with non-smokers, erythrocytes from smokers were more susceptible to hydrogen peroxide-induced lipid peroxidation in vitro. 5. Vitamin E supplementation further increased erythrocyte catalase (EC 1.11.1.6) activity in both smokers and non-smokers (P < 0.001) and erythrocyte glutathione peroxidase (EC 1.11.1.9) and glutathione reductase (EC 1.6.4.2) activities in non-smokers (P < 0.001). After supplementation with vitamin E there was a concomitant fall in erythrocyte superoxide dismutase (EC 1.15.1.1) activity (P < 0.001) and total glutathione concentration (P < 0.01). Furthermore, in both smokers and non-smokers there was a significant decrease in the susceptibility of erythrocytes to peroxidation (P < 0.001). 6. Various endogenous and exogenous factors exert control over cellular protection against reactive oxygen species, and our data suggest that one such factor is the supply of vitamin E.
