Oxidation of glutathione and cysteine in human plasma associated with smoking.

Cigarette smoking contributes to the development or progression of numerous chronic and age-related disease processes, but detailed mechanisms remain elusive. In the present study, we examined the redox states of the GSH/GSSG and Cys/CySS couples in plasma of smokers and nonsmokers between the ages of 44 and 85 years (n = 78 nonsmokers, n = 43 smokers). The Cys/CySS redox in smokers (-64 +/- 16 mV) was more oxidized than nonsmokers (- 76 +/- 11 mV; p <.001), with decreased Cys in smokers (9 +/- 5 microM) compared to nonsmokers (13 +/- 6 microM; p <.001). The GSH/GSSG redox was also more oxidized in smokers (-128 +/- 18 mV) than in nonsmokers (-137 +/- 17 mV; p =.01) and GSH was lower in smokers (1.8 +/- 1.3 microM) than in nonsmokers (2.4 +/- 1.0; p <.005). Although the oxidation of GSH/GSSG can be explained by the role of GSH in detoxification of reactive species in smoke, the more extensive oxidation of the Cys pool shows that smoking has additional effects on sulfur amino acid metabolism. Cys availability and Cys/CySS redox are known to affect cell proliferation, immune function, and expression of death receptor systems for apoptosis, suggesting that oxidation of Cys/CySS redox or other perturbations of cysteine metabolism may have a key role in chronic diseases associated with cigarette smoking.