Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases.
Cigarette smoke causes significant oxidant stress which is further enhanced by recruitment and activation of inflammatory cells to the lung. Polymorphisms in some detoxification enzymes are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD), but the ultimate role of genetic variability in antioxidant and/or detoxification enzymes in COPD remains obscure. Some antioxidant enzymes are inducted, but the extent of induction is insufficient to protect the lung/alveolar epithelium against cigarette smoke. Exogenous antioxidants such as vitamins do not seem to protect against cigarette smoke related lung injury. Glutathione related synthetic drugs such as N-acetylcysteine have shown some benefits, but they may have pro-oxidant side effects. Synthetic compounds with superoxide dismutase and catalase activities have shown promising results in animal models against a variety of oxidant exposures including cigarette smoke in the lung. These results are in agreement with studies highlighting the importance of alveolar antioxidant protection mechanisms in oxidant stress and their inducibility. These new drugs need to be tested in cigarette smoking related lung injury/inflammation since inflammation/oxidant stress can continue after discontinuation of smoking.
Kinnula
V L
VL
University of Helsinki, Department of Medicine, Pulmonary Division, P O Box 22, Haartmaninkatu 4, Helsinki, FI-00014, Finland. vuokko.kinnula@helsinki.fi
D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008171:Lung Diseases / Q000201:enzymology* / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase