Strategies to decrease ongoing oxidant burden in chronic obstructive pulmonary disease

References

• Buist AS, McBurnie MA, Vollmer WM et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet370(9589), 741–750 (2007).
   PubMed Web of Science ®Google Scholar
• Hu G, Zhou Y, Tian J et al. Risk of COPD from exposure to biomass smoke: a meta-analysis. Chest138(1), 20–31 (2010).
   PubMed Web of Science ®Google Scholar
• Pillai SG, Kong X, Edwards LD et al. Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.182(12), 1498–1505 (2010).
   PubMed Web of Science ®Google Scholar
• Eisner MD, Anthonisen N, Coultas D et al. An official American thoracic society public policy statement: novel risk factors and the global burden of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.182(5), 693–718 (2010).
   PubMed Web of Science ®Google Scholar
• Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax59(7), 574–580 (2004).
   PubMed Web of Science ®Google Scholar
• Wouters EF, Reynaert NL, Dentener MA, Vernooy JH. Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection? Proc. Am. Thorac. Soc.6(8), 638–647 (2009).
   PubMedGoogle Scholar
• Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J.28(1), 219–242 (2006).
   PubMed Web of Science ®Google Scholar
• Rabe KF, Hurd S, Anzueto A et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respir. Crit. Care Med.176(6), 532–555 (2007).
   PubMed Web of Science ®Google Scholar
• Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu. Rev. Pathol.4, 435–459 (2009).
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet378(9795), 1015–1026 (2011).
   PubMed Web of Science ®Google Scholar
• Martinez FJ, Donohue JF, Rennard SI. The future of chronic obstructive pulmonary disease treatment – difficulties of and barriers to drug development. Lancet378(9795), 1027–1037 (2011).
   PubMed Web of Science ®Google Scholar
• Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in nonsmokers. Lancet374(9691), 733–743 (2009).
   PubMed Web of Science ®Google Scholar
• Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, PostmaDS, Timens W. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur. Respir. J.26(5), 835–845 (2005).
   PubMed Web of Science ®Google Scholar
• Gamble E, Grootendorst DC, Hattotuwa K et al. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur. Respir. J.30(3), 467–471 (2007).
   PubMed Web of Science ®Google Scholar
• Louhelainen N, Rytila P, Haahtela T, Kinnula VL, Djukanovic R. Persistence of oxidant and protease burden in the airways after smoking cessation. BMC Pulm. Med.9, 25 (2009).
   PubMedGoogle Scholar
• Louhelainen N, Stark H, Mazur W, Rytila P, Djukanovic R, Kinnula VL. Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study. BMC Pulm. Med.10, 13 (2010).
   PubMedGoogle Scholar
• Rahman I, Kinnula VL, Gorbunova V, Yao H. SIRT1 as a therapeutic target in inflammaging of the pulmonary disease. Prev. Med. doi:10.1016/j.ypmed.2011.11.014 (2011) (Epub ahead of print).
   Google Scholar
• Elkington PT, Friedland JS. Matrix metalloproteinases in destructive pulmonary pathology. Thorax61(3), 259–266 (2006).
   PubMed Web of Science ®Google Scholar
• MacNee W. Accelerated lung aging: a novel pathogenic mechanism of chronic obstructive pulmonary disease (COPD). Biochem. Soc. Trans.37(Pt 4), 819–823 (2009).
   PubMed Web of Science ®Google Scholar
• Yao H, Rahman I. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol. Appl. Pharmacol.254(2), 72–85 (2011).
   PubMed Web of Science ®Google Scholar
• Koli K, Myllarniemi M, Keski-Oja J, Kinnula VL. Transforming growth factor-β activation in the lung: focus on fibrosis and reactive oxygen species. Antioxid. Redox. Signal10(2), 333–342 (2008).
   PubMed Web of Science ®Google Scholar
• Barnes PJ, Chowdhury B, Kharitonov SA et al. Pulmonary biomarkers in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.174(1), 6–14 (2006).
   PubMed Web of Science ®Google Scholar
• Kharitonov S, Alving K, Barnes PJ. Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur. Respir. J.10(7), 1683–1693 (1997).
   PubMed Web of Science ®Google Scholar
• Rahman I, Biswas SK. Noninvasive biomarkers of oxidative stress: reproducibility and methodological issues. Redox. Rep.9(3), 125–143 (2004).
   PubMed Web of Science ®Google Scholar
• Louhelainen N, Myllarniemi M, Rahman I, Kinnula VL. Airway biomarkers of the oxidant burden in asthma and chronic obstructive pulmonary disease: current and future perspectives. Int. J. Chron. Obstruct. Pulmon. Dis.3(4), 585–603 (2008).
   PubMedGoogle Scholar
• Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet370(9589), 797–799 (2007).
   PubMed Web of Science ®Google Scholar
• Church DF, Pryor WA. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect.64, 111–126 (1985).
   PubMed Web of Science ®Google Scholar
• Pryor WA, Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann. NY Acad. Sci.686, 12–27 (1993).
   PubMed Web of Science ®Google Scholar
• Saetta M, Baraldo S, Zuin R. Neutrophil chemokines in severe exacerbations of chronic obstructive pulmonary disease: fatal chemoattraction? Am. J. Respir. Crit. Care Med.168(8), 911–913 (2003).
   PubMedGoogle Scholar
• Kinnula VL, Crapo JD, Raivio KO. Generation and disposal of reactive oxygen metabolites in the lung. Lab. Invest.73(1), 3–19 (1995).
   PubMed Web of Science ®Google Scholar
• Byers DE, Holtzman MJ. Alternatively activated macrophages and airway disease. Chest140(3), 768–774 (2011).
   PubMed Web of Science ®Google Scholar
• Papi A, Romagnoli M, Baraldo S et al. Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.162(5), 1773–1777 (2000).
   PubMed Web of Science ®Google Scholar
• Hogg JC, Chu F, Utokaparch S et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med.350(26), 2645–2653 (2004).
   PubMed Web of Science ®Google Scholar
• Kirkham PA, Caramori G, Casolari P et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.184(7), 796–802 (2011).
   PubMed Web of Science ®Google Scholar
• Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax64(8), 728–735 (2009).
   PubMed Web of Science ®Google Scholar
• Djukanovic R, Sterk PJ, Fahy JV, Hargreave FE. Standardised methodology of sputum induction and processing. Eur. Respir. J. Suppl.37, S1–S2 (2002).
   PubMedGoogle Scholar
• Gompertz S, Bayley DL, Hill SL, Stockley RA. Relationship between airway inflammation and the frequency of exacerbations in patients with smoking-related COPD. Thorax56(1), 36–41 (2001).
   PubMed Web of Science ®Google Scholar
• Aaron SD, Angel JB, Lunau M et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.163(2), 349–355 (2001).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Ilumets H, Myllarniemi M, Sovijarvi A, Rytila P. 8-isoprostane as a marker of oxidative stress in nonsymptomatic cigarette smokers and COPD. Eur. Respir. J.29(1), 51–55 (2007).
   PubMed Web of Science ®Google Scholar
• Montuschi P, Collins JV, Ciabattoni G et al. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am. J. Respir. Crit. Care Med.162(3 Pt 1), 1175–1177 (2000).
   PubMed Web of Science ®Google Scholar
• Rahman I, van Schadewijk AA, Crowther AJ et al. 4-hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.166(4), 490–495 (2002).
   PubMed Web of Science ®Google Scholar
• Rytila P, Rehn T, Ilumets H et al. Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD. Respir. Res.7, 69 (2006).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Am. J. Respir. Crit. Care Med.167(12), 1600–1619 (2003).
   PubMed Web of Science ®Google Scholar
• Biswas SK, Rahman I. Environmental toxicity, redox signaling and lung inflammation: the role of glutathione. Mol. Aspects Med.30(1–2), 60–76 (2009).
   PubMed Web of Science ®Google Scholar
• Cantin AM, North SL, Hubbard RC, Crystal RG. Normal alveolar epithelial lining fluid contains high levels of glutathione. J. Appl. Physiol.63(1), 152–157 (1987).
   PubMed Web of Science ®Google Scholar
• Oury TD, Day BJ, Crapo JD. Extracellular superoxide dismutase: a regulator of nitric oxide bioavailability. Lab. Invest.75(5), 617–636 (1996).
   PubMed Web of Science ®Google Scholar
• Lakari E, Paakko P, Kinnula VL. Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Am. J. Respir. Crit. Care Med.158(2), 589–596 (1998).
   PubMed Web of Science ®Google Scholar
• Lakari E, Paakko P, Pietarinen-Runtti P, Kinnula VL. Manganese superoxide dismutase and catalase are coordinately expressed in the alveolar region in chronic interstitial pneumonias and granulomatous diseases of the lung. Am. J. Respir. Crit. Care Med.161(2 Pt 1), 615–621 (2000).
   PubMed Web of Science ®Google Scholar
• Oury TD, Chang LY, Marklund SL, Day BJ, Crapo JD. Immunocytochemical localization of extracellular superoxide dismutase in human lung. Lab. Invest.70(6), 889–898 (1994).
   PubMed Web of Science ®Google Scholar
• Wong GH, Goeddel DV. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science242(4880), 941–944 (1988).
   PubMed Web of Science ®Google Scholar
• Gilks CB, Price K, Wright JL, Churg A. Antioxidant gene expression in rat lung after exposure to cigarette smoke. Am. J. Pathol.152(1), 269–278 (1998).
   PubMed Web of Science ®Google Scholar
• MacMillan-Crow LA, Crow JP, Thompson JA. Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues. Biochemistry37(6), 1613–1622 (1998).
   PubMed Web of Science ®Google Scholar
• Comhair SA, Xu W, Ghosh S et al. Superoxide dismutase inactivation in pathophysiology of asthmatic airway remodeling and reactivity. Am. J. Pathol.166(3), 663–674 (2005).
   PubMed Web of Science ®Google Scholar
• Li Y, Huang TT, Carlson EJ et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat. Genet.11(4), 376–381 (1995).
   PubMed Web of Science ®Google Scholar
• Foronjy RF, Mirochnitchenko O, Propokenko O et al. Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice. Am. J. Respir. Crit. Care Med.173(6), 623–631 (2006).
   PubMed Web of Science ®Google Scholar
• Brady TC, Chang LY, Day BJ, Crapo JD. Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-κB activation. Am. J. Physiol.273(5 Pt 1), L1002–L1006 (1997).
   PubMedGoogle Scholar
• Carlsson LM, Jonsson J, Edlund T, Marklund SL. Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc. Natl Acad. Sci. USA92(14), 6264–6268 (1995).
   PubMed Web of Science ®Google Scholar
• Yao H, Arunachalam G, Hwang JW et al. Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM. Proc. Natl Acad. Sci. USA107(35), 15571–15576 (2010).
   PubMed Web of Science ®Google Scholar
• Gongora MC, Lob HE, Landmesser U et al. Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome. Am. J. Pathol.173(4), 915–926 (2008).
   PubMed Web of Science ®Google Scholar
• Folz RJ, Abushamaa AM, Suliman HB. Extracellular superoxide dismutase in the airways of transgenic mice reduces inflammation and attenuates lung toxicity following hyperoxia. J. Clin. Invest.103(7), 1055–1066 (1999).
   PubMed Web of Science ®Google Scholar
• Pietarinen P, Raivio K, Devlin RB, Crapo JD, Chang LY, Kinnula VL. Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro. Am. J. Respir. Cell. Mol. Biol.13(4), 434–441 (1995).
   PubMed Web of Science ®Google Scholar
• Mossman BT, Marsh JP, Sesko A et al. Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis. Am. Rev. Respir. Dis.141(5 Pt 1), 1266–1271 (1990).
   PubMed Web of Science ®Google Scholar
• Rahman I, Biswas SK, Jimenez LA, Torres M, Forman HJ. Glutathione, stress responses, and redox signaling in lung inflammation. Antioxid. Redox Signal7(1–2), 42–59 (2005).
   PubMed Web of Science ®Google Scholar
• Comhair SA, Bhathena PR, Farver C, Thunnissen FB, Erzurum SC. Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells. FASEB J.15(1), 70–78 (2001).
   PubMed Web of Science ®Google Scholar
• Soini Y, Napankangas U, Jarvinen K, Kaarteenaho-Wiik R, Paakko P, Kinnula VL. Expression of γ-glutamyl cysteine synthetase in non-small-cell lung carcinoma. Cancer92(11), 2911–2919 (2001).
   PubMed Web of Science ®Google Scholar
• Harju T, Mazur W, Merikallio H, Soini Y, Kinnula VL. Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity. Respir. Res.9, 80 (2008).
   PubMedGoogle Scholar
• Aesif SW, Anathy V, Havermans M et al.In situ analysis of protein S-glutathionylation in lung tissue using glutaredoxin-1-catalyzed cysteine derivatization. Am. J. Pathol.175(1), 36–45 (2009).
   PubMed Web of Science ®Google Scholar
• Aesif SW, Kuipers I, van der Velden J et al. Activation of the glutaredoxin-1 gene by nuclear factor-κB enhances signaling. Free Radic. Biol. Med.51(6), 1249–1257 (2011).
   PubMed Web of Science ®Google Scholar
• Peltoniemi M, Kaarteenaho-Wiik R, Saily M et al. Expression of glutaredoxin is highly cell specific in human lung and is decreased by transforming growth factor-β in vitro and in interstitial lung diseases in vivo. Hum. Pathol.35(8), 1000–1007 (2004).
   PubMedGoogle Scholar
• Kuipers I, Guala AS, Aesif SW et al. Cigarette smoke targets glutaredoxin 1, increasing S-glutathionylation and epithelial cell death. Am. J. Respir. Cell. Mol. Biol.45(5), 931–937 (2011).
   PubMed Web of Science ®Google Scholar
• Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1–Nrf2–ARE pathway. Annu. Rev. Pharmacol. Toxicol.47, 89–116 (2007).
   PubMed Web of Science ®Google Scholar
• Rangasamy T, Guo J, Mitzner WA et al. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J. Exp. Med.202(1), 47–59 (2005).
   PubMed Web of Science ®Google Scholar
• Sussan TE, Rangasamy T, Blake DJ et al. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc. Natl Acad. Sci. USA106(1), 250–255 (2009).
   PubMed Web of Science ®Google Scholar
• Giudice A, Arra C, Turco MC. Review of molecular mechanisms involved in the activation of the Nrf2–ARE signaling pathway by chemopreventive agents. Methods Mol. Biol.647, 37–74 (2010).
   PubMedGoogle Scholar
• Singh A, Rangasamy T, Thimmulappa RK et al. Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2. Am. J. Respir. Cell. Mol. Biol.35(6), 639–650 (2006).
   PubMed Web of Science ®Google Scholar
• Rangasamy T, Cho CY, Thimmulappa RK et al. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J. Clin. Invest.114(9), 1248–1259 (2004).
   PubMed Web of Science ®Google Scholar
• Iizuka T, Ishii Y, Itoh K et al. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema. Genes Cells10(12), 1113–1125 (2005).
   PubMed Web of Science ®Google Scholar
• Holmgren A. Antioxidant function of thioredoxin and glutaredoxin systems. Antioxid. Redox Signal2(4), 811–820 (2000).
   PubMed Web of Science ®Google Scholar
• Tiitto L, Kaarteenaho-Wiik R, Sormunen R et al. Expression of the thioredoxin system in interstitial lung disease. J. Pathol.201(3), 363–370 (2003).
   PubMed Web of Science ®Google Scholar
• Soini Y, Kahlos K, Napankangas U et al. Widespread expression of thioredoxin and thioredoxin reductase in non-small-cell lung carcinoma. Clin. Cancer Res.7(6), 1750–1757 (2001).
   PubMed Web of Science ®Google Scholar
• Li Y, Liu W, Xing G, Tian C, Zhu Y, He F. Direct association of hepatopoietin with thioredoxin constitutes a redox signal transduction in activation of AP-1/NF-κB. Cell Signal17(8), 985–996 (2005).
   PubMedGoogle Scholar
• Sato A, Hoshino Y, Hara T et al. Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice. J. Pharmacol. Exp. Ther.325(2), 380–388 (2008).
   PubMed Web of Science ®Google Scholar
• Rhee SG, Kang SW, Netto LE, Seo MS, Stadtman ER. A family of novel peroxidases, peroxiredoxins. Biofactors10(2–3), 207–209 (1999).
   PubMed Web of Science ®Google Scholar
• Wood ZA, Schroder E, Robin Harris J, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci.28(1), 32–40 (2003).
   PubMed Web of Science ®Google Scholar
• Mo Y, Feinstein SI, Manevich Y et al. 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly related intronless gene. FEBS Lett.555(2), 192–198 (2003).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Lehtonen S, Kaarteenaho-Wiik R et al. Cell-specific expression of peroxiredoxins in human lung and pulmonary sarcoidosis. Thorax57(2), 157–164 (2002).
   PubMed Web of Science ®Google Scholar
• Lehtonen ST, Svensk AM, Soini Y et al. Peroxiredoxins, a novel protein family in lung cancer. Int. J. Cancer111(4), 514–521 (2004).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Lehtonen S, Sormunen R et al. Overexpression of peroxiredoxins I, II, III, V and VI in malignant mesothelioma. J. Pathol.196(3), 316–323 (2002).
   PubMed Web of Science ®Google Scholar
• Neumann CA, Krause DS, Carman CV et al. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature424(6948), 561–565 (2003).
   PubMed Web of Science ®Google Scholar
• Sundar IK, Chung S, Hwang JW et al. Peroxiredoxin-6 differentially regulates acute and chronic cigarette smoke-mediated lung inflammatory response and injury. Exp. Lung Res.36(8), 451–462 (2010).
   PubMed Web of Science ®Google Scholar
• Rhee SG, Woo HA. Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger HO, and protein chaperones. Antioxid. Redox Signal15(3), 781–794 (2011).
   PubMed Web of Science ®Google Scholar
• Park JW, Mieyal JJ, Rhee SG, Chock PB. Deglutathionylation of 2-Cys peroxiredoxin is specifically catalyzed by sulfiredoxin. J. Biol. Chem.284(35), 23364–23374 (2009).
   PubMed Web of Science ®Google Scholar
• Chang TS, Jeong W, Woo HA, Lee SM, Park S, Rhee SG. Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine. J. Biol. Chem.279(49), 50994–51001 (2004).
   PubMed Web of Science ®Google Scholar
• Baek JY, Han SH, Sung SH et al. Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2. J. Biol. Chem.287(1), 81–89 (2012).
   PubMedGoogle Scholar
• Mazur W, Lindholm P, Vuorinen K, Myllarniemi M, Salmenkivi K, Kinnula VL. Cell-specific elevation of Nrf2 and sulfiredoxin-1 as markers of oxidative stress in the lungs of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. APMIS118(9), 703–712 (2010).
   PubMedGoogle Scholar
• Singh A, Ling G, Suhasini AN et al. Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs. Free Radic. Biol. Med.46(3), 376–386 (2009).
   PubMed Web of Science ®Google Scholar
• Hackett NR, Heguy A, Harvey BG et al. Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am. J. Respir. Cell. Mol. Biol.29(3 Pt 1), 331–343 (2003).
   PubMed Web of Science ®Google Scholar
• Pierrou S, Broberg P, O’Donnell RA et al. Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.175(6), 577–586 (2007).
   PubMed Web of Science ®Google Scholar
• Harju T, Kaarteenaho-Wiik R, Sirvio R et al. Manganese superoxide dismutase is increased in the airways of smokers’ lungs. Eur. Respir. J.24(5), 765–771 (2004).
   PubMed Web of Science ®Google Scholar
• Regan EA, Mazur W, Meoni E et al. Smoking and COPD increase sputum levels of extracellular superoxide dismutase. Free Radic. Biol. Med.51(3), 726–732 (2011).
   PubMed Web of Science ®Google Scholar
• Goven D, Boutten A, Lecon-Malas V et al. Altered Nrf2/Keap1–Bach1 equilibrium in pulmonary emphysema. Thorax63(10), 916–924 (2008).
   PubMed Web of Science ®Google Scholar
• Malhotra D, Thimmulappa R, Navas-Acien A et al. Decline in Nrf2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am. J. Respir. Crit. Care Med.178(6), 592–604 (2008).
   PubMed Web of Science ®Google Scholar
• Suzuki M, Betsuyaku T, Ito Y et al. Downregulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am. J. Respir. Cell. Mol. Biol.39(6), 673–682 (2008).
   PubMed Web of Science ®Google Scholar
• Blake DJ, Singh A, Kombairaju P et al. Deletion of Keap1 in the lung attenuates acute cigarette smoke-induced oxidative stress and inflammation. Am. J. Respir. Cell. Mol. Biol.42(5), 524–536 (2010).
   PubMed Web of Science ®Google Scholar
• Comhair SA, Erzurum SC. The regulation and role of extracellular glutathione peroxidase. Antioxid. Redox Signal7(1–2), 72–79 (2005).
   PubMed Web of Science ®Google Scholar
• Comhair SA, Lewis MJ, Bhathena PR et al. Increased glutathione and glutathione peroxidase in lungs of individuals with chronic beryllium disease. Am. J. Respir. Crit. Care Med.159(6), 1824–1829 (1999).
   PubMedGoogle Scholar
• Golpon HA, Coldren CD, Zamora MR et al. Emphysema lung tissue gene expression profiling. Am. J. Respir. Cell Mol. Biol.31(6), 595–600 (2004).
   PubMed Web of Science ®Google Scholar
• Rahman I, van Schadewijk AA, Hiemstra PS et al. Localization of γ-glutamylcysteine synthetase messenger RNA expression in lungs of smokers and patients with chronic obstructive pulmonary disease. Free Radic. Biol. Med.28(6), 920–925 (2000).
   PubMed Web of Science ®Google Scholar
• Harju T, Kaarteenaho-Wiik R, Soini Y, Sormunen R, Kinnula VL. Diminished immunoreactivity of γ-glutamylcysteine synthetase in the airways of smokers’ lung. Am. J. Respir. Crit. Care Med.166(5), 754–759 (2002).
   PubMed Web of Science ®Google Scholar
• Soini Y, Kaarteenaho-Wiik R, Paakko P, Kinnula V. Expression of antioxidant enzymes in bronchial metaplastic and dysplastic epithelium. Lung Cancer39(1), 15–22 (2003).
   PubMedGoogle Scholar
• Harju TH, Peltoniemi MJ, Rytila PH et al. Glutathione S-transferase ω in the lung and sputum supernatants of COPD patients. Respir. Res.8, 48 (2007).
   PubMedGoogle Scholar
• Peltoniemi MJ, Rytila PH, Harju TH et al. Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease. Respir. Res.7, 133 (2006).
   PubMedGoogle Scholar
• Maestrelli P, El Messlemani AH, De Fina O et al. Increased expression of heme oxygenase (HO)-1 in alveolar spaces and HO-2 in alveolar walls of smokers. Am. J. Respir. Crit. Care Med.164(8 Pt 1), 1508–1513 (2001).
   PubMed Web of Science ®Google Scholar
• Maestrelli P, Paska C, Saetta M et al. Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients. Eur. Respir. J.21(6), 971–976 (2003).
   PubMed Web of Science ®Google Scholar
• Lehtonen ST, Ohlmeier S, Kaarteenaho-Wiik R et al. Does the oxidative stress in chronic obstructive pulmonary disease cause thioredoxin/peroxiredoxin oxidation? Antioxid. Redox Signal.10(4), 813–819 (2008).
   PubMed Web of Science ®Google Scholar
• Lee EJ, In KH, Kim JH et al. Proteomic analysis in lung tissue of smokers and COPD patients. Chest135(2), 344–352 (2009).
   PubMed Web of Science ®Google Scholar
• Malhotra D, Thimmulappa RK, Mercado N et al. Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients. J. Clin. Invest.121(11), 4289–4302 (2011).
   PubMed Web of Science ®Google Scholar
• Lawes CM, Thornley S, Young R et al. Statin use in COPD patients is associated with a reduction in mortality: a national cohort study. Prim. Care Respir. J.21(1), 35–40 (2012).
   PubMedGoogle Scholar
• Huang CC, Chan WL, Chen YC et al. Statin use and hospitalization in patients with chronic obstructive pulmonary disease: a nationwide population-based cohort study in Taiwan. Clin. Ther.33(10), 1365–1370 (2011).
   PubMed Web of Science ®Google Scholar
• Makita H, Nasuhara Y, Nagai K et al. Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease. Thorax62(11), 932–937 (2007).
   PubMed Web of Science ®Google Scholar
• Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur. Respir. J.16(2), 253–262 (2000).
   PubMed Web of Science ®Google Scholar
• Decramer M, Dekhuijzen PN, Troosters T et al. The Bronchitis Randomized on NAC Cost–Utility Study (BRONCUS): hypothesis and design. BRONCUS trial committee. Eur. Respir. J.17(3), 329–336 (2001).
   PubMed Web of Science ®Google Scholar
• Decramer M, Rutten-van Molken M, Dekhuijzen PN et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost–Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet365(9470), 1552–1560 (2005).
   PubMed Web of Science ®Google Scholar
• Poole PJ, Black PN. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. BMJ322(7297), 1271–1274 (2001).
   PubMed Web of Science ®Google Scholar
• Poole PJ, Black PN. Preventing exacerbations of chronic bronchitis and COPD: therapeutic potential of mucolytic agents. Am. J. Respir. Med.2(5), 367–370 (2003).
   PubMedGoogle Scholar
• Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin. Ther.22(2), 209–221 (2000).
   PubMed Web of Science ®Google Scholar
• Black PN, Morgan-Day A, McMillan TE, Poole PJ, Young RP. Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344]. BMC Pulm. Med.4, 13 (2004).
   PubMedGoogle Scholar
• Moretti M, Bottrighi P, Dallari R et al. The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE study. Drugs Exp. Clin. Res.30(4), 143–152 (2004).
   PubMedGoogle Scholar
• Zheng JP, Kang J, Huang SG et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE study): a randomised placebo-controlled study. Lancet371(9629), 2013–2018 (2008).
   PubMed Web of Science ®Google Scholar
• Gillissen A, Jaworska M, Orth M et al. Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir. Med.91(3), 159–168 (1997).
   PubMed Web of Science ®Google Scholar
• Moretti M. Pharmacology and clinical efficacy of erdosteine in chronic obstructive pulmonary disease. Expert Rev. Respir. Med.1(3), 307–316 (2007).
   PubMedGoogle Scholar
• Moretti M. Erdosteine: its relevance in COPD treatment. Expert Opin. Drug Metab. Toxicol.5(3), 333–343 (2009).
   PubMed Web of Science ®Google Scholar
• Cazzola M, Floriani I, Page CP. The therapeutic efficacy of erdosteine in the treatment of chronic obstructive bronchitis: a meta-analysis of individual patient data. Pulm. Pharmacol. Ther.23(2), 135–144 (2010).
   PubMed Web of Science ®Google Scholar
• Braga PC, Allegra L, Rampoldi C, Ornaghi A, Beghi G. Long-lasting effects on rheology and clearance of bronchial mucus after short-term administration of high doses of carbocysteine–lysine to patients with chronic bronchitis. Respiration57(6), 353–358 (1990).
   PubMed Web of Science ®Google Scholar
• Cakan G, Turkoz M, Turan T, Ahmed K, Nagatake T. S-carboxymethylcysteine inhibits the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells. Microb. Pathog.34(6), 261–265 (2003).
   PubMed Web of Science ®Google Scholar
• Tatsumi K, Fukuchi Y. Carbocisteine improves quality of life in patients with chronic obstructive pulmonary disease. J. Am. Geriatr. Soc.55(11), 1884–1886 (2007).
   PubMed Web of Science ®Google Scholar
• Aylward M. An assessment of S-carboxymethylcysteine in the treatment of chronic bronchitis. Curr. Med. Res. Opin.2(7), 387–394 (1974).
   PubMed Web of Science ®Google Scholar
• Edwards GF, Steel AE, Scott JK, Jordan JW. S-carboxymethylcysteine in the fluidification of sputum and treatment of chronic airway obstruction. Chest70(4), 506–513 (1976).
   PubMed Web of Science ®Google Scholar
• Miskoviti G, Szule P, Mescaros K. Double-blind study of carbocysteine against placebo in chronic bronchitis; mucoregulation in respiratory tract disorders. Proc. R. Soc. Med.5, 1–3 (1982).
   Google Scholar
• Allegra L, Cordaro CI, Grassi C. Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial. Respiration63(3), 174–180 (1996).
   PubMed Web of Science ®Google Scholar
• Grillage M, Barnard-Jones K. Long-term oral carbocisteine therapy in patients with chronic bronchitis. A double blind trial with placebo control. Br. J. Clin. Pract.39(10), 395–398 (1985).
   PubMedGoogle Scholar
• Yasuda H, Yamaya M, Sasaki T et al. Carbocisteine reduces frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease. J. Am. Geriatr. Soc.54(2), 378–380 (2006).
   PubMed Web of Science ®Google Scholar
• Yasuda H, Yamaya M, Sasaki T et al. Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells. Eur. Respir. J.28(1), 51–58 (2006).
   PubMed Web of Science ®Google Scholar
• Rhee CK, Kang CM, You MB et al. Effect of fudosteine on mucin production. Eur. Respir. J.32(5), 1195–1202 (2008).
   PubMed Web of Science ®Google Scholar
• Komatsu H, Yamaguchi S, Komorita N et al. Inhibition of endotoxin- and antigen-induced airway inflammation by fudosteine, a mucoactive agent. Pulm. Pharmacol. Ther.18(2), 121–127 (2005).
   PubMed Web of Science ®Google Scholar
• Nagaoka S, Takishima T, Nagano H et al. Phase III clinical study of SS320A. Double-blind trial in comparison with placebo. J. Clin. Ther. Med.18(1), 109–140 (2002).
   Google Scholar
• Ekberg-Jansson A, Larson M, MacNee W et al.N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis. Eur. Respir. J.13(4), 829–834 (1999).
   PubMed Web of Science ®Google Scholar
• Moncaster JA, Walsh DT, Gentleman SM, Jen LS, Aruoma OI. Ergothioneine treatment protects neurons against N-methyl-D-aspartate excitotoxicity in an in vivo rat retinal model. Neurosci. Lett.328(1), 55–59 (2002).
   PubMed Web of Science ®Google Scholar
• Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res.62(18), 5196–5203 (2002).
   PubMed Web of Science ®Google Scholar
• Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1–Nrf2 pathway. Identification of novel gene clusters for cell survival. J. Biol. Chem.278(10), 8135–8145 (2003).
   PubMed Web of Science ®Google Scholar
• Balogun E, Hoque M, Gong P et al. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem. J.371(Pt 3), 887–895 (2003).
   PubMed Web of Science ®Google Scholar
• Go ML, Wu X, Liu XL. Chalcones: an update on cytotoxic and chemoprotective properties. Curr. Med. Chem.12(4), 481–499 (2005).
   PubMed Web of Science ®Google Scholar
• Wei BL, Teng CH, Wang JP, Won SJ, Lin CN. Synthetic 2´,5´-dimethoxychalcones as G(2)/M arrest-mediated apoptosis-inducing agents and inhibitors of nitric oxide production in rat macrophages. Eur. J. Med. Chem.42(5), 660–668 (2007).
   PubMed Web of Science ®Google Scholar
• Lee JH, Jung HS, Giang PM et al. Blockade of nuclear factor-κB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. J. Pharmacol. Exp. Ther.316(1), 271–278 (2006).
   PubMed Web of Science ®Google Scholar
• Kumar V, Kumar S, Hassan M et al. Novel chalcone derivatives as potent Nrf2 activators in mice and human lung epithelial cells. J. Med. Chem.54(12), 4147–4159 (2011).
   PubMed Web of Science ®Google Scholar
• Tajima S, Bando M, Ishii Y et al. Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice. Eur. Respir. J.32(5), 1337–1343 (2008).
   PubMedGoogle Scholar
• Kikuchi K, Uchikado H, Miyagi N et al. Beyond neurological disease: new targets for edaravone (review). Int. J. Mol. Med.28(6), 899–906 (2011).
   PubMed Web of Science ®Google Scholar
• Aldini G, Vistoli G, Regazzoni L, Benfatto MC, Bettinelli I, Carini M. Edaravone inhibits protein carbonylation by a direct carbonyl-scavenging mechanism: focus on reactivity, selectivity, and reaction mechanisms. Antioxid. Redox Signal.12(3), 381–392 (2010).
   PubMed Web of Science ®Google Scholar
• Ito K, Ozasa H, Horikawa S. Edaravone protects against lung injury induced by intestinal ischemia/reperfusion in rat. Free Radic. Biol. Med.38(3), 369–374 (2005).
   PubMed Web of Science ®Google Scholar
• Aldini G, Dalle-Donne I, Facino RM, Milzani A, Carini M. Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonyls. Med. Res. Rev.27(6), 817–868 (2007).
   PubMed Web of Science ®Google Scholar
• Aldini G, Dalle-Donne I, Colombo R, Maffei Facino R, Milzani A, Carini M. Lipoxidation-derived reactive carbonyl species as potential drug targets in preventing protein carbonylation and related cellular dysfunction. Chem. Med. Chem.1(10), 1045–1058 (2006).
   Web of Science ®Google Scholar
• Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science321(5895), 1493–1495 (2008).
   PubMed Web of Science ®Google Scholar
• Braughler JM, Pregenzer JF, Chase RL, Duncan LA, Jacobsen EJ, McCall JM. Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation. J. Biol. Chem.262(22), 10438–10440 (1987).
   PubMed Web of Science ®Google Scholar
• Miniati M, Cocci F, Monti S et al. Lazaroid U-74389F attenuates phorbol ester-induced lung injury in rabbits. Eur. Respir. J.9(4), 758–764 (1996).
   PubMedGoogle Scholar
• Tuder RM, Zhen L, Cho CY et al. Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. Am. J. Respir. Cell. Mol. Biol.29(1), 88–97 (2003).
   PubMed Web of Science ®Google Scholar
• Muscoli C, Sacco I, Alecce W et al. The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: role of the lectin-like oxidized low-density lipoprotein receptor-1. J. Pharmacol. Exp. Ther.311(1), 44–50 (2004).
   PubMedGoogle Scholar
• Chang LY, Crapo JD. Inhibition of airway inflammation and hyper-reactivity by an antioxidant mimetic. Free Radic. Biol. Med.33(3), 379–386 (2002).
   PubMed Web of Science ®Google Scholar
• Smith KR, Uyeminami DL, Kodavanti UP, Crapo JD, Chang LY, Pinkerton KE. Inhibition of tobacco smoke-induced lung inflammation by a catalytic antioxidant. Free Radic. Biol. Med.33(8), 1106–1114 (2002).
   PubMed Web of Science ®Google Scholar
• Sharpe MA, Ollosson R, Stewart VC, Clark JB. Oxidation of nitric oxide by oxomanganese–salen complexes: a new mechanism for cellular protection by superoxide dismutase/catalase mimetics. Biochem. J.366(Pt 1), 97–107 (2002).
   PubMed Web of Science ®Google Scholar
• Day BJ, Shawen S, Liochev SI, Crapo JD. A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury in vitro. J. Pharmacol. Exp. Ther.275(3), 1227–1232 (1995).
   PubMed Web of Science ®Google Scholar
• Day BJ, Fridovich I, Crapo JD. Manganic porphyrins possess catalase activity and protect endothelial cells against hydrogen peroxide-mediated injury. Arch. Biochem. Biophys.347(2), 256–262 (1997).
   PubMed Web of Science ®Google Scholar
• Ferrer-Sueta G, Vitturi D, Batinic-Haberle I et al. Reactions of manganese porphyrins with peroxynitrite and carbonate radical anion. J. Biol. Chem.278(30), 27432–27438 (2003).
   PubMed Web of Science ®Google Scholar
• Tse HM, Milton MJ, Piganelli JD. Mechanistic analysis of the immunomodulatory effects of a catalytic antioxidant on antigen-presenting cells: implication for their use in targeting oxidation–reduction reactions in innate immunity. Free Radic. Biol. Med.36(2), 233–247 (2004).
   PubMed Web of Science ®Google Scholar
• Vujaskovic Z, Batinic-Haberle I, Rabbani ZN et al. A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Radic. Biol. Med.33(6), 857–863 (2002).
   PubMed Web of Science ®Google Scholar
• Piganelli JD, Flores SC, Cruz C et al. A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone. Diabetes51(2), 347–355 (2002).
   PubMed Web of Science ®Google Scholar
• Zhang HJ, Doctrow SR, Xu L et al. Redox modulation of the liver with chronic antioxidant enzyme mimetic treatment prevents age-related oxidative damage associated with environmental stress. FASEB J.18(13), 1547–1549 (2004).
   PubMed Web of Science ®Google Scholar
• Zhang HJ, Doctrow SR, Oberley LW, Kregel KC. Chronic antioxidant enzyme mimetic treatment differentially modulates hyperthermia-induced liver HSP70 expression with aging. J. Appl. Physiol.100(4), 1385–1391 (2006).
   PubMed Web of Science ®Google Scholar
• Souza DG, Vieira AT, Pinho V et al. NF-κB plays a major role during the systemic and local acute inflammatory response following intestinal reperfusion injury. Br. J. Pharmacol.145(2), 246–254 (2005).
   PubMed Web of Science ®Google Scholar
• Nguyen C, Teo JL, Matsuda A et al. Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma. Proc. Natl Acad. Sci. USA100(3), 1169–1173 (2003).
   PubMedGoogle Scholar
• Bachnoff N, Trus M, Atlas D. Alleviation of oxidative stress by potent and selective thioredoxin-mimetic peptides. Free Radic. Biol. Med.50(10), 1355–1367 (2011).
   PubMedGoogle Scholar
• Stefanutti G, Pierro A, Smith VV, Klein NJ, Eaton S. Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats. Pediatr. Res.62(1), 43–48 (2007).
   PubMedGoogle Scholar
• Pacher P, Liaudet L, Bai P et al. Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction. Circulation107(6), 896–904 (2003).
   PubMed Web of Science ®Google Scholar
• Cuzzocrea S, Thiemermann C, Salvemini D. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr. Med. Chem.11(9), 1147–1162 (2004).
   PubMed Web of Science ®Google Scholar
• Shi H, Timmins G, Monske M et al. Evaluation of spin trapping agents and trapping conditions for detection of cell-generated reactive oxygen species. Arch. Biochem. Biophys.437(1), 59–68 (2005).
   PubMedGoogle Scholar
• Osoata GO, Yamamura S, Ito M et al. Nitration of distinct tyrosine residues causes inactivation of histone deacetylase-2. Biochem. Biophys. Res. Commun.384(3), 366–371 (2009).
   PubMed Web of Science ®Google Scholar
• Nott A, Watson PM, Robinson JD, Crepaldi L, Riccio A. S-nitrosylation of histone deacetylase-2 induces chromatin remodelling in neurons. Nature455(7211), 411–415 (2008).
   PubMed Web of Science ®Google Scholar
• Valenca SS, Rueff-Barroso CR, Pimenta WA et al.L-NAME and L-arginine differentially ameliorate cigarette smoke-induced emphysema in mice. Pulm. Pharmacol. Ther.24(5), 587–594 (2011).
   PubMed Web of Science ®Google Scholar
• Seimetz M, Parajuli N, Pichl A et al. Inducible NOS inhibition reverses tobacco smoke-induced emphysema and pulmonary hypertension in mice. Cell147(2), 293–305 (2011).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Crapo JD. Superoxide dismutases in malignant cells and human tumors. Free Radic. Biol. Med.36(6), 718–744 (2004).
   PubMed Web of Science ®Google Scholar
• Kinnula VL, Paakko P, Soini Y. Antioxidant enzymes and redox regulating thiol proteins in malignancies of human lung. FEBS Lett.569(1–3), 1–6 (2004).
   PubMed Web of Science ®Google Scholar