Cigarette Smoke-Induced Oxidant/Antioxidant Imbalance and its Role in Increased Epithelial Permeability

Abstract

An imbalance between oxidants and antioxidants is proposed in the pathogenesis of the smoking-related lung disease—chronic obstructive pulmonary disease (COPD) (Rahman and MacNee, 1996). Cigarette smoke, contains 10 oxidant molecules per puff, (Pryor et al., 1993) producing an enormous oxidant burden on the lungs. In addition to the oxidants in cigarette smoke, the numbers of inflammatory leukocytes are increased in the airspaces of cigarette smokers compared with non-smokers (Hunninghake, 1983), which release more reactive oxygen species (ROS) (Shaberg et al., 1992). In addition neutrophils, sequestered in the pulmonary circulation during cigarette smoking (MacNee et al., 1989), may release more ROS (Brown et al., 1995). All tissues are vulnerable to oxidant damage but by virtue of its location, the airspace epithelium is particularly vulnerable. Studies in healthy smokers (Jones et al., 1980) have shown an increased epithelial permeability, measured by increased clearance from the lungs of technetium 99m-labelled diethylenetriamine pentaacetic acid (Tc-DTPA). There is limited information on the antioxidant defences of the respiratory tract epithelial lining fluid in smokers (Cross et al., 1994). The important thiol antioxidant glutathione (GSH) is increased in the epithelial lining fluid in the airways of chronic smokers (Cantin et al., 1987) and appears to be related to humoral markers of inflammatory cell activity (Linden et al., 1989). Glutathione may have an important role in protecting the epithelium from the effects of oxidant-induced injury produced by cigarette smoke. The aims of this study were to assess the oxidant/antioxidant imbalance produced by cigarette smoke and to determine the role of the antioxidant glutathione in the increased epithelial permeability produced by cigarette smoke.