Clin Chem Lab Med 2011;49(12):2007–2012  2011 by Walter de Gruyter • Berlin • Boston. DOI 10.1515/CCLM.2011.698 2011/0261 Article in press - uncorrected proof Oxidative status in the lungs associated with tobacco smoke exposure Sibel Doruk 1, *, Huseyin Ozyurt 2 , Handan Inonu 1 , Unal Erkorkmaz 3 , Oguzhan Saylan 2 and Zehra Seyfikli 4 1 Department of Pulmonary Medicine, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey 2 Department of Biochemistry, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey 3 Department of Biostatistics, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey 4 Cumhuriyet University Faculty of Medicine, Department of Pulmonary Medicine, Sivas, Turkey Abstract Background: Oxidative stress has a critical role in inflam- matory responce against tobacco smoke (TS). Testing exhaled breath condensate (EBC) samples is one of the meth- ods used for assessment of airway inflammation caused by TS. We aimed to investigate oxidative stress in the lungs associated with TS and to evaluate the effect of this stress with pulmonary function tests (PFTs). Methods: We included 69 subjects as three groups into the study (Group I; 26 smokers, Group II; 21 passive smokers, Group III; 22 non-smokers without TS exposure). Levels of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8- OHdG), nitrite/nitrate w index of nitric oxide (NO) produc- tionx , vitamin C, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were measured in EBC samples collected using a condenser and PFTs were performed. Results: The levels of MDA, 8-OHdG, SOD and GSH-Px were higher in smokers. NO levels gradually increased from Group I to Group III. MDA levels were lower in Group III than Group II. The levels of vitamin C were similar in all groups. We determined negative correlation between 8-OHdG levels and forced expiratory volume in one second (FEV 1 ), and maximum mean expiratory flow (MMEF), and a positive correlation between SOD levels and FEV 1 . Conclusions: TS exposure affected the balance between oxi- dative stress and antioxidant capacity of lungs. Preventing environmental TS exposure might decrease oxidative dam- age. Increased levels of 8-OHdG and SOD levels could be assessed as an early sign of airway damage. *Corresponding author: Assoc. Prof. Dr. Sibel Doruk, Gaziosmanpasa University Faculty of Medicine, Department of Pulmonary Medicine, 60100 Tokat, Turkey Phone: q903562129500 (1310), Fax: q903562133179, E-mail: sibeldoruk@yahoo.com Received April 28, 2011; accepted July 27, 2011; previously published online September 13, 2011 Keywords: antioxidant status; environmental tobacco smoke; exhaled breath condensate; oxidative stress; smoking; tobacco smoke. Introduction Cigarette smoking is the most common type of tobacco use and in 2020 the global burden is expected to exceed nine million deaths annually (1, 2). Cigarette smoke (CS) is a complex mixture of chemical compounds and smoking is associated with increased oxidative stress in the lungs. There are many studies in the literature reporting an increase in lipid peroxidation and in the release of oxygen radicals, decreased antioxidant capacity and an imbalance of oxidant/ antioxidant status in smokers (3, 4). Oxidative stress can be assessed and monitored through the determination of the levels of biomarkers in different biological samples, such as serum, bronchoalveolar lavage fluid (BALF), induced sputum, bronchial biopsy and exhaled breath condensate (EBC). Collection of EBC liquid phase of the exhaled air sampled by cooling is a non-invasive method and can reflect acid stress, oxidative stress and inflammation (5–7). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are the most effective enzymatic antioxidants. The activity of GSH-Px appears to be an important feature in determining oxidative damage (8). Another antioxidant limits oxidative damage in humans is vitamin C (9, 10). Malondialdehyde (MDA) and nitric oxid (NO) are toxic products associated with lipid peroxidation and react with protein and DNA (11, 12). Analyses of MDA in EBC is a reliable index of airway oxidative stress (13). An alternative biomarker of oxidative DNA damage asso- ciated with chemical exposure is 8-OHdG and 8-OHdG dem- onstrates the balance between DNA formation and repair (12–15). Oxidative stress markers have been demonstrated in the epithelial lining fluid (ELF), breath, urine and blood (3). Several antioxidants including SOD, catalase, GSH-Px, and vitamins are present in the lungs to counteract the oxidant mediated toxicity and these antioxidants provide a first line defense against inhaled, also endogenously produced oxi- dants (16, 17). There are many important effects of oxidative stress in smokers which may be critical for the inflammatory response to CS (3). Previous studies have indicated that smokers have higher levels of biomarkers of oxidative stress compared to non-smokers (18, 19). The detection of oxidant and antiox- idant markers may reflect the effect of CS on the oxidative- antioxidative balance in the lungs. We aimed to determine Brought to you by | Karolinska Institute Authenticated Download Date | 5/30/15 12:39 AM