A significant number of potentially cytotoxic compounds (e.g., carbon monoxide, free radicals and their precursors, nitrosamines, phenolic compounds, and other polynuclear aromatic compounds [119]), are found in the gas and particulate phases of cigarette smoke, which may be directly cytotoxic, damage neuronal or glial cell organelles and promote oxidative damage ([120], Muscat, 2004 #13479, [121,122]). For example, carbon monoxide (CO) levels are significantly higher in smokers [123], and this elevation is associated with decreased effective hemoglobin concentrations, diminished oxygen carrying capacity of erythrocytes [124], as well as a diminished efficiency of the mitochondrial respiratory chain [125]. Furthermore, cigarette smoke also contains high concentrations of free radical species (e.g., reactive nitrogen species; reactive oxygen species, ROS) known to promote oxidative damage or stress to cellular structures as well as to macromolecules including membrane lipids, proteins, carbohydrates and DNA [126]. The radical species in the particulate matter of cigarette smoke are long-lived (i.e., hours to months) compared to those in the gas phase [5], and can compromise organs other than the lungs [120,127]. In vivo chronic exposure of rat brain tissue to
