The Role of Oxidative Stress in Smoking-Related Diseases

Oxidative stress, the accumulation of oxygen free radicals (reactive oxygen species) above and beyond the capacity of a cell to utilise antioxidant systems to detoxify these potentially damaging molecules, is a common feature of many human disorders. Cigarette smoke is not only a source of free radicals but is also a potent stimulator of the intracellular production of free radicals, by the mitochondrial electron transport chain and the plasmalemmal NADPH oxidase. Adding to this free radical burden is the reduction, by cigarette smoke, of the cellular antioxidant capacity. Together, the increased production and reduced detoxification of free radicals has been strongly linked to smoking-induced diseases including atherosclerotic cardiovascular disease, cancer and chronic obstructive pulmonary disease (COPD). In this review, we discuss the mechanisms underlying cellular free radical production, relate this to the three major smoking-related human diseases listed above and present potential mechanisms by which cigarette smoke may increase the oxidative burden on cells and contribute to disease.