Oxidative and Nitrosative Stress in the Pathogenesis of Obstructive Lung Diseases of Increasing Severity

Antonino       Di Stefano; Mauro       Maniscalco; Bruno       Balbi; Fabio    L.M.    Ricciardolo

doi:10.2174/0929867327666200604165451

Abstract

The imbalance between increased oxidative agents and antioxidant defence mechanisms is central in the pathogenesis of obstructive lung diseases such as asthma and COPD. In these patients, there are increased levels of reactive oxygen species. Superoxide anions (O₂ -), Hydrogen Peroxide (H₂O₂) and hydroxyl radicals (•OH) are critical for the formation of further cytotoxic radicals in the bronchi and lung parenchyma. Chronic inflammation, partly induced by oxidative stress, can further increase the oxidant burden through activated phagocytic cells (neutrophils, eosinophils, macrophages), particularly in severer disease states. Antioxidants and anti-inflammatory genes are, in fact, frequently downregulated in diseased patients. Nrf2, which activates the Antioxidant Response Element (ARE) leading to upregulation of GPx, thiol metabolism-associated detoxifying enzymes (GSTs) and stressresponse genes (HO-1) are all downregulated in animal models and patients with asthma and COPD. An exaggerated production of Nitric Oxide (NO) in the presence of oxidative stress can promote the formation of oxidizing reactive nitrogen species, such as peroxynitrite (ONO₂ -), leading to nitration and DNA damage, inhibition of mitochondrial respiration, protein dysfunction, and cell damage in the biological systems. Protein nitration also occurs by activation of myeloperoxidase and H₂O₂, promoting oxidation of nitrite (NO₂ -). There is increased nitrotyrosine and myeloperoxidase in the bronchi of COPD patients, particularly in severe disease. The decreased peroxynitrite inhibitory activity found in induced sputum of COPD patients correlates with pulmonary function. Markers of protein nitration - 3- nitrotyrosine, 3-bromotyrosine, and 3-chlorotyrosine - are increased in the bronchoalveolar lavage of severe asthmatics. Targeting the oxidative, nitrosative stress and associated lung inflammation through the use of either denitration mechanisms or new drug delivery strategies for antioxidant administration could improve the treatment of these chronic disabling obstructive lung diseases.

Keywords: Oxidative stress, asthma, COPD, inflammation, nitrosative stress, pathogenesis.

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[1] 
Andreadis, A.A.; Hazen, S.L.; Comhair, S.A.; Erzurum, S.C. Oxidative and nitrosative events in asthma. Free Radic. Biol. Med.,  2003, 35(3), 213-225.
[http://dx.doi.org/10.1016/S0891-5849(03)00278-8] [PMID: 12885584] 
[2] 
Ricciardolo, F.L.; Di Stefano, A.; Sabatini, F.; Folkerts, G. Reactive nitrogen species in the respiratory tract. Eur. J. Pharmacol.,  2006, 533(1-3), 240-252.
[http://dx.doi.org/10.1016/j.ejphar.2005.12.057] [PMID: 16464450] 
[3] 
Dozor, A.J. The role of oxidative stress in the pathogenesis and treatment of asthma. Ann. N. Y. Acad. Sci.,  2010, 1203, 133-137.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05562.x] [PMID: 20716295] 
[4] 
Antus, B.; Kardos, Z. Oxidative stress in COPD: molecular background and clinical monitoring. Curr. Med. Chem.,  2015, 22(5), 627-650.
[http://dx.doi.org/10.2174/092986732205150112104411] [PMID: 25585265] 
[5] 
Soodaeva, S.; Kubysheva, N.; Klimanov, I.; Nikitina, L.; Batyrshin, I. Features of oxidative and nitrosative metabolism in lung diseases. Oxid. Med. Cell. Longev.,  2019, 2019(1), 1-12.
[http://dx.doi.org/10.1155/2019/1689861] 
[6] 
Ricciardolo, F.L.; Sterk, P.J.; Gaston, B.; Folkerts, G. Nitric oxide in health and disease of the respiratory system. Physiol. Rev.,  2004, 84(3), 731-765.
[http://dx.doi.org/10.1152/physrev.00034.2003] [PMID: 15269335] 
[7] 
Folkerts, G.; Kloek, J.; Muijsers, R.B.; Nijkamp, F.P. Reactive nitrogen and oxygen species in airway inflammation. Eur. J. Pharmacol.,  2001, 429(1-3), 251-262.
[http://dx.doi.org/10.1016/S0014-2999(01)01324-3] [PMID: 11698045] 
[8] 
Squadrito, G.L.; Pryor, W.A. Mapping the reaction of peroxynitrite with CO2: energetics, reactive species, and biological implications. Chem. Res. Toxicol.,  2002, 15(7), 885-895.
[http://dx.doi.org/10.1021/tx020004c] [PMID: 12118998] 
[9] 
Lemercier, J.N.; Padmaja, S.; Cueto, R.; Squadrito, G.L.; Uppu, R.M.; Pryor, W.A. Carbon dioxide modulation of hydroxylation and nitration of phenol by peroxynitrite. Arch. Biochem. Biophys.,  1997, 345(1), 160-170.
[http://dx.doi.org/10.1006/abbi.1997.0240] [PMID: 9281324] 
[10] 
Babior, B.M. NADPH oxidase. Curr. Opin. Immunol.,  2004, 16(1), 42-47.
[http://dx.doi.org/10.1016/j.coi.2003.12.001] [PMID: 14734109] 
[11] 
Topic, A.; Milovanovic, V.; Lazic, Z.; Ivosevic, A.; Radojkovic, D. Oxidized alpha-1-antitrypsin as a potential biomarker associated with onset and severity of chronic obstructive pulmonary disease in adult population. COPD,  2018, 15(5), 472-478.
[http://dx.doi.org/10.1080/15412555.2018.1541448] [PMID: 30822244] 
[12] 
Lıu, X.; Deng, K.; Chen, S.; Zhang, Y.; Yao, J.; Weng, X.; Zhang, Y.; Gao, T.; Feng, G. 8-Hydroxy-2′-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease. Turk. J. Med. Sci.,  2019, 49(1), 93-100.
[http://dx.doi.org/10.3906/sag-1807-106] [PMID: 30762093] 
[13] 
Tang, K.; Zhao, J.; Xie, J.; Wang, J. Decreased miR-29b expression is associated with airway inflammation in chronic obstructive pulmonary disease. Am. J. Physiol. Lung Cell. Mol. Physiol.,  2019, 316(4), L621-L629.
[http://dx.doi.org/10.1152/ajplung.00436.2018] [PMID: 30652495] 
[14] 
Taka, C.; Hayashi, R.; Shimokawa, K.; Tokui, K.; Okazawa, S.; Kambara, K.; Inomata, M.; Yamada, T.; Matsui, S.; Tobe, K. SIRT1 and FOXO1 mRNA expression in PBMC correlates to physical activity in COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis.,  2017, 12, 3237-3244.
[http://dx.doi.org/10.2147/COPD.S144969] [PMID: 29138552] 
[15] 
Sanders, K.A.; Delker, D.A.; Huecksteadt, T.; Beck, E.; Wuren, T.; Chen, Y.; Zhang, Y.; Hazel, M.W.; Hoidal, J.R. RAGE is a critical mediator of pulmonary oxidative stress, alveolar macrophage activation and emphysema in response to cigarette smoke. Sci. Rep.,  2019, 9(1), 231.
[http://dx.doi.org/10.1038/s41598-018-36163-z] [PMID: 30659203] 
[16] 
Kuhn, V.; Diederich, L.; Keller, T.C.S., IV; Kramer, C.M.; Lückstädt, W.; Panknin, C.; Suvorava, T.; Isakson, B.E.; Kelm, M.; Cortese-Krott, M.M. Red Blood cell function and dysfunction: redox regulation, nitric oxide metabolism, anemia. Antioxid. Redox Signal.,  2017, 26(13), 718-742.
[http://dx.doi.org/10.1089/ars.2016.6954] [PMID: 27889956] 
[17] 
Saleh, D.; Ernst, P.; Lim, S.; Barnes, P.J.; Giaid, A. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid. FASEB J.,  1998, 12(11), 929-937.
[http://dx.doi.org/10.1096/fasebj.12.11.929] [PMID: 9707165] 
[18] 
Ricciardolo, F.L.; Caramori, G.; Ito, K.; Capelli, A.; Brun, P.; Abatangelo, G.; Papi, A.; Chung, K.F.; Adcock, I.; Barnes, P.J.; Donner, C.F.; Rossi, A.; Di Stefano, A. Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease. J. Allergy Clin. Immunol.,  2005, 116(5), 1028-1035.
[http://dx.doi.org/10.1016/j.jaci.2005.06.034] [PMID: 16275371] 
[19] 
van der Vliet, A.; Eiserich, J.P.; Shigenaga, M.K.; Cross, C.E. Reactive nitrogen species and tyrosine nitration in the respiratory tract: epiphenomena or a pathobiologic mechanism of disease? Am. J. Respir. Crit. Care Med.,  1999, 160(1), 1-9.
[http://dx.doi.org/10.1164/ajrccm.160.1.9807044] [PMID: 10390372] 
[20] 
Marozkina, N.V.; Gaston, B. Nitrogen chemistry and lung physiology. Annu. Rev. Physiol.,  2015, 77, 431-452.
[http://dx.doi.org/10.1146/annurev-physiol-021113-170352] [PMID: 25668023] 
[21] 
Fang, F.C. Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J. Clin. Invest.,  1997, 99(12), 2818-2825.
[http://dx.doi.org/10.1172/JCI119473] [PMID: 9185502] 
[22] 
Radi, R.; Cassina, A.; Hodara, R.; Quijano, C.; Castro, L. Peroxynitrite reactions and formation in mitochondria. Free Radic. Biol. Med.,  2002, 33(11), 1451-1464.
[http://dx.doi.org/10.1016/S0891-5849(02)01111-5] [PMID: 12446202] 
[23] 
Eiserich, J.P.; Estévez, A.G.; Bamberg, T.V.; Ye, Y.Z.; Chumley, P.H.; Beckman, J.S.; Freeman, B.A. Microtubule dysfunction by posttranslational nitrotyrosination of alpha-tubulin: a nitric oxide-dependent mechanism of cellular injury. Proc. Natl. Acad. Sci. USA,  1999, 96(11), 6365-6370.
[http://dx.doi.org/10.1073/pnas.96.11.6365] [PMID: 10339593] 
[24] 
Shibuya, A.; Wada, K.; Nakajima, A.; Saeki, M.; Katayama, K.; Mayumi, T.; Kadowaki, T.; Niwa, H.; Kamisaki, Y. Nitration of PPARgamma inhibits ligand-dependent translocation into the nucleus in a macrophage-like cell line, RAW 264. FEBS Lett.,  2002, 525(1-3), 43-47.
[http://dx.doi.org/10.1016/S0014-5793(02)03059-4] [PMID: 12163159] 
[25] 
Kamisaki, Y.; Wada, K.; Bian, K.; Balabanli, B.; Davis, K.; Martin, E.; Behbod, F.; Lee, Y.C.; Murad, F. An activity in rat tissues that modifies nitrotyrosine-containing proteins. Proc. Natl. Acad. Sci. USA,  1998, 95(20), 11584-11589.
[http://dx.doi.org/10.1073/pnas.95.20.11584] [PMID: 9751709] 
[26] 
Zingarelli, B.; O’Connor, M.; Wong, H.; Salzman, A.L.; Szabó, C. Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysac-charide. J. Immunol.,  1996, 156(1), 350-358.
[PMID: 8598485] 
[27] 
O’Donnell, V.B.; Eiserich, J.P.; Bloodsworth, A.; Chumley, P.H.; Kirk, M.; Barnes, S.; Darley-Usmar, V.M.; Freeman, B.A. Nitration of unsaturated fatty acids by nitric oxide-derived reactive species. Methods Enzymol.,  1999, 301, 454-470.
[http://dx.doi.org/10.1016/S0076-6879(99)01109-X] [PMID: 9919594] 
[28] 
Packer, M.A.; Murphy, M.P. Peroxynitrite formed by simultaneous nitric oxide and superoxide generation causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation. Eur. J. Biochem.,  1995, 234(1), 231-239.
[http://dx.doi.org/10.1111/j.1432-1033.1995.231_c.x] [PMID: 8529645] 
[29] 
Zhu, S.; Haddad, I.Y.; Matalon, S. Nitration of surfactant protein A (SP-A) tyrosine residues results in decreased mannose binding ability. Arch. Biochem. Biophys.,  1996, 333(1), 282-290.
[http://dx.doi.org/10.1006/abbi.1996.0392] [PMID: 8806782] 
[30] 
Gow, A.J.; Chen, Q.; Hess, D.T.; Day, B.J.; Ischiropoulos, H.; Stamler, J.S. Basal and stimulated protein S-nitrosylation in multiple cell types and tissues. J. Biol. Chem.,  2002, 277(12), 9637-9640.
[http://dx.doi.org/10.1074/jbc.C100746200] [PMID: 11796706] 
[31] 
Okamoto, T.; Akuta, T.; Tamura, F.; van Der Vliet, A.; Akaike, T. Molecular mechanism for activation and regulation of matrix met-alloproteinases during bacterial infections and respiratory inflammation. Biol. Chem.,  2004, 385(11), 997-1006.
[http://dx.doi.org/10.1515/BC.2004.130] [PMID: 15576319] 
[32] 
Whiteman, M.; Szabó, C.; Halliwell, B. Modulation of peroxynitrite- and hypochlorous acid-induced inactivation of alpha1-antiproteinase by mercaptoethylguanidine. Br. J. Pharmacol.,  1999, 126(7), 1646-1652.
[http://dx.doi.org/10.1038/sj.bjp.0702465] [PMID: 10323598] 
[33] 
Filep, J.G.; Beauchamp, M.; Baron, C.; Paquette, Y. Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood. J. Immunol.,  1998, 161(10), 5656-5662.
[PMID: 9820546] 
[34] 
Payne, D.N.; Adcock, I.M.; Wilson, N.M.; Oates, T.; Scallan, M.; Bush, A. Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone. Am. J. Respir. Crit. Care Med.,  2001, 164(8 Pt 1), 1376-1381.
[http://dx.doi.org/10.1164/ajrccm.164.8.2101145] [PMID: 11704581] 
[35] 
Schleich, F.N.; Zanella, D.; Stefanuto, P.H.; Bessonov, K.; Smolinska, A.; Dallinga, J.W.; Henket, M.; Paulus, V.; Guissard, F.; Graff, S.; Moermans, C.; Wouters, E.F.M.; Van Steen, K.; van Schooten, F.J.; Focant, J.F.; Louis, R. Exhaled volatile organic compounds are able to discriminate between neutrophilic and eosinophilic asthma. Am. J. Respir. Crit. Care Med.,  2019, 200(4), 444-453.
[http://dx.doi.org/10.1164/rccm.201811-2210OC] [PMID: 30973757] 
[36] 
Ricciardolo, F.L.; Geppetti, P.; Mistretta, A.; Nadel, J.A.; Sapienza, M.A.; Bellofiore, S.; Di Maria, G.U. Randomised double-blind placebo-controlled study of the effect of inhibition of nitric oxide synthesis in bradykinin-induced asthma. Lancet,  1996, 348(9024), 374-377.
[http://dx.doi.org/10.1016/S0140-6736(96)04450-9] [PMID: 8709736] 
[37] 
Ricciardolo, F.L.; Timmers, M.C.; Geppetti, P.; van Schadewijk, A.; Brahim, J.J.; Sont, J.K.; de Gouw, H.W.; Hiemstra, P.S.; van Krieken, J.H.; Sterk, P.J. Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma. J. Allergy Clin. Immunol.,  2001, 108(2), 198-204.
[http://dx.doi.org/10.1067/mai.2001.116572] [PMID: 11496234] 
[38] 
MacPherson, J.C.; Comhair, S.A.; Erzurum, S.C.; Klein, D.F.; Lipscomb, M.F.; Kavuru, M.S.; Samoszuk, M.K.; Hazen, S.L. Eosino-phils are a major source of nitric oxide-derived oxidants in severe asthma: characterization of pathways available to eosinophils for generating reactive nitrogen species. J. Immunol.,  2001, 166(9), 5763-5772.
[http://dx.doi.org/10.4049/jimmunol.166.9.5763] [PMID: 11313420] 
[39] 
Chaudhuri, R.; Livingston, E.; McMahon, A.D.; Lafferty, J.; Fraser, I.; Spears, M.; McSharry, C.P.; Thomson, N.C. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am. J. Respir. Crit. Care Med.,  2006, 174(2), 127-133.
[http://dx.doi.org/10.1164/rccm.200510-1589OC] [PMID: 16645173] 
[40] 
Kharitonov, S.A.; Robbins, R.A.; Yates, D.; Keatings, V.; Barnes, P.J. Acute and chronic effects of cigarette smoking on exhaled nitric oxide. Am. J. Respir. Crit. Care Med.,  1995, 152(2), 609-612.
[http://dx.doi.org/10.1164/ajrccm.152.2.7543345] [PMID: 7543345] 
[41] 
Agustí, A.G.; Villaverde, J.M.; Togores, B.; Bosch, M. Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease. Eur. Respir. J.,  1999, 14(3), 523-528.
[http://dx.doi.org/10.1034/j.1399-3003.1999.14c08.x] [PMID: 10543270] 
[42] 
Kharitonov, S.A.; Barnes, P.J. Nitric oxide, nitrotyrosine and nitric oxide modulators in asthma and chronic obstructive pulmonary disease. Curr. Allergy Asthma Rep.,  2003, 3(2), 121-129.
[http://dx.doi.org/10.1007/s11882-003-0024-7] [PMID: 12562551] 
[43] 
Sugiura, H.; Ichinose, M. Nitrative stress in inflammatory lung diseases. Nitric Oxide,  2011, 25(2), 138-144.
[http://dx.doi.org/10.1016/j.niox.2011.03.079] [PMID: 21440655] 
[44] 
Indo, H.P.; Yen, H.C.; Nakanishi, I.; Matsumoto, K.; Tamura, M.; Nagano, Y.; Matsui, H.; Gusev, O.; Cornette, R.; Okuda, T.; Minamiyama, Y.; Ichikawa, H.; Suenaga, S.; Oki, M.; Sato, T.; Ozawa, T.; Clair, D.K.; Majima, H.J. A mitochondrial superoxide theory for oxidative stress diseases and aging. J. Clin. Biochem. Nutr.,  2015, 56(1), 1-7.
[http://dx.doi.org/10.3164/jcbn.14-42] [PMID: 25834301] 
[45] 
Vézina, F.A.; Cantin, A.M. Antioxidants and chronic obstructive pulmonary disease. Chronic Obstr. Pulm. Dis. (Miami),  2018, 5(4), 277-288.
[http://dx.doi.org/10.15326/jcopdf.5.4.2018.0133] [PMID: 30723785] 
[46] 
Borgstahl, G.E.; Parge, H.E.; Hickey, M.J.; Johnson, M.J.; Boissinot, M.; Hallewell, R.A.; Lepock, J.R.; Cabelli, D.E.; Tainer, J.A. Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface. Biochemistry,  1996, 35(14), 4287-4297.
[http://dx.doi.org/10.1021/bi951892w] [PMID: 8605177] 
[47] 
Gardner, P.R.; Raineri, I.; Epstein, L.B.; White, C.W. Superoxide radical and iron modulate aconitase activity in mammalian cells. J. Biol. Chem.,  1995, 270(22), 13399-13405.
[http://dx.doi.org/10.1074/jbc.270.22.13399] [PMID: 7768942] 
[48] 
Chelikani, P.; Carpena, X.; Perez-Luque, R.; Donald, L.J.; Duckworth, H.W.; Switala, J.; Fita, I.; Loewen, P.C. Characterization of a large subunit catalase truncated by proteolytic cleavage. Biochemistry,  2005, 44(15), 5597-5605.
[http://dx.doi.org/10.1021/bi047277m] [PMID: 15823018] 
[49] 
Pader, I.; Sengupta, R.; Cebula, M.; Xu, J.; Lundberg, J.O.; Holmgren, A.; Johansson, K.; Arnér, E.S. Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase. Proc. Natl. Acad. Sci. USA,  2014, 111(19), 6964-6969.
[http://dx.doi.org/10.1073/pnas.1317320111] [PMID: 24778250] 
[50] 
Deponte, M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim. Biophys. Acta,  2013, 1830(5), 3217-3266.
[http://dx.doi.org/10.1016/j.bbagen.2012.09.018] [PMID: 23036594] 
[51] 
Sharapov, M.G.; Novoselov, V.I. Catalytic and signaling role of peroxiredoxins in carcinogenesis. Biochemistry (Mosc.),  2019, 84(2), 79-100.
[http://dx.doi.org/10.1134/S0006297919020019] [PMID: 31216969] 
[52] 
Levine, M.; Padayatty, S.J.; Espey, M.G. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr.,  2011, 2(2), 78-88.
[http://dx.doi.org/10.3945/an.110.000109] [PMID: 22332036] 
[53] 
Cadenas, E.; Packer, L.; Traber, M.G. Antioxidants, oxidants and redox impacts on cell function - a tribute to Helmut Sies. Arch. Biochem. Biophys.,  2016, 595, 94-99.
[http://dx.doi.org/10.1016/j.abb.2015.11.012] [PMID: 27095223] 
[54] 
Millea, P.J. N-acetylcysteine: multiple clinical applications. Am. Fam. Physician,  2009, 80(3), 265-269.
[PMID: 19621836] 
[55] 
Kelly, G. The interaction of cigarette smoking and antioxidants. Part III: ascorbic acid. Altern. Med. Rev.,  2003, 8(1), 43-54.
[PMID: 12611560] 
[56] 
Parodi, O.; De Maria, R.; Roubina, E. Redox state, oxidative stress and endothelial dysfunction in heart failure: the puzzle of nitrate-thiol interaction. J. Cardiovasc. Med. (Hagerstown),  2007, 8(10), 765-774.
[http://dx.doi.org/10.2459/JCM.0b013e32801194d4] [PMID: 17885513] 
[57] 
Santus, P.; Corsico, A.; Solidoro, P.; Braido, F.; Di Marco, F.; Scichilone, N. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD,  2014, 11(6), 705-717.
[http://dx.doi.org/10.3109/15412555.2014.898040] [PMID: 24787454] 
[58] 
Janssens, W.; Mathieu, C.; Boonen, S.; Decramer, M. Vitamin D deficiency and chronic obstructive pulmonary disease: a vicious circle. Vitam. Horm.,  2011, 86, 379-399.
[http://dx.doi.org/10.1016/B978-0-12-386960-9.00017-4] [PMID: 21419281] 
[59] 
Calzetta, L.; Matera, M.G.; Rogliani, P.; Cazzola, M. Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. Expert Rev. Respir. Med.,  2018, 12(8), 693-708.
[http://dx.doi.org/10.1080/17476348.2018.1495562] [PMID: 29972340] 
[60] 
Fowdar, K.; Chen, H.; He, Z.; Zhang, J.; Zhong, X.; Zhang, J.; Li, M.; Bai, J. The effect of N-acetylcysteine on exacerbations of chronic obstructive pulmonary disease: A meta-analysis and systematic review. Heart Lung,  2017, 46(2), 120-128.
[http://dx.doi.org/10.1016/j.hrtlng.2016.12.004] [PMID: 28109565] 
[61] 
Zeng, Z.; Yang, D.; Huang, X.; Xiao, Z. Effect of carbocisteine on patients with COPD: a systematic review and meta-analysis. Int. J. Chron. Obstruct. Pulmon. Dis.,  2017, 12, 2277-2283.
[http://dx.doi.org/10.2147/COPD.S140603] [PMID: 28814855] 
[62] 
Biswas, S.; Hwang, J.W.; Kirkham, P.A.; Rahman, I. Pharmacological and dietary antioxidant therapies for chronic obstructive pul-monary disease. Curr. Med. Chem.,  2013, 20(12), 1496-1530.
[http://dx.doi.org/10.2174/0929867311320120004] [PMID: 22963552] 
[63] 
Poole, P.; Sathananthan, K.; Fortescue, R. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev.,  2019, 5(5)CD001287
[http://dx.doi.org/10.1002/14651858.CD001287.pub6] [PMID: 31107966] 
[64] 
Moretti, M.; Bottrighi, P.; Dallari, R.; Da Porto, R.; Dolcetti, A.; Grandi, P.; Garuti, G.; Guffanti, E.; Roversi, P.; De Gugliemo, M.; Potena, A. EQUALIFE Study Group The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE Study. Drugs Exp. Clin. Res.,  2004, 30(4), 143-152.
[PMID: 15553660] 
[65] 
Negro, D.R.; Pozzi, E.; Cella, S.G. Erdosteine: Drug exhibiting polypharmacy for the treatment of respiratory diseases. Pulm. Pharmacol. Ther.,  2018, 53, 80-85.
[http://dx.doi.org/10.1016/j.pupt.2018.10.005] [PMID: 30352285] 
[66] 
Hodge, S.; Matthews, G.; Mukaro, V.; Ahern, J.; Shivam, A.; Hodge, G.; Holmes, M.; Jersmann, H.; Reynolds, P.N. Cigarette smoke-induced changes to alveolar macrophage phenotype and function are improved by treatment with procysteine. Am. J. Respir. Cell Mol. Biol.,  2011, 44(5), 673-681.
[http://dx.doi.org/10.1165/rcmb.2009-0459OC] [PMID: 20595463] 
[67] 
Tanabe, N.; Hoshino, Y.; Marumo, S.; Kiyokawa, H.; Sato, S.; Kinose, D.; Uno, K.; Muro, S.; Hirai, T.; Yodoi, J.; Mishima, M. Thi-oredoxin-1 protects against neutrophilic inflammation and emphysema progression in a mouse model of chronic obstructive pulmonary disease exacerbation. PLoS One,  2013, 8(11)e79016
[http://dx.doi.org/10.1371/journal.pone.0079016] [PMID: 24244404] 
[68] 
Liu, Q.; Gao, Y.; Ci, X. Role of Nrf2 and its activators in respiratory diseases. Oxid. Med. Cell. Longev.,  2019, 20197090534
[http://dx.doi.org/10.1155/2019/7090534] [PMID: 30728889] 
[69] 
Zhao, H.; Eguchi, S.; Alam, A.; Ma, D. The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol.,  2017, 312(2), L155-L162.
[http://dx.doi.org/10.1152/ajplung.00449.2016] [PMID: 27864288] 
[70] 
Vunta, H.; Davis, F.; Palempalli, U.D.; Bhat, D.; Arner, R.J.; Thompson, J.T.; Peterson, D.G.; Reddy, C.C.; Prabhu, K.S. The anti-inflammatory effects of selenium are mediated through 15-deoxy-Delta12,14-prostaglandin J2 in macrophages. J. Biol. Chem.,  2007, 282(25), 17964-17973.
[http://dx.doi.org/10.1074/jbc.M703075200] [PMID: 17439952] 
[71] 
Sussan, T.E.; Rangasamy, T.; Blake, D.J.; Malhotra, D.; El-Haddad, H.; Bedja, D.; Yates, M.S.; Kombairaju, P.; Yamamoto, M.; Liby, K.T.; Sporn, M.B.; Gabrielson, K.L.; Champion, H.C.; Tuder, R.M.; Kensler, T.W.; Biswal, S. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc. Natl. Acad. Sci. USA,  2009, 106(1), 250-255.
[http://dx.doi.org/10.1073/pnas.0804333106] [PMID: 19104057] 
[72] 
Wise, R.A.; Holbrook, J.T.; Criner, G.; Sethi, S.; Rayapudi, S.; Sudini, K.R.; Sugar, E.A.; Burke, A.; Thimmulappa, R.; Singh, A.; Talalay, P.; Fahey, J.W.; Berenson, C.S.; Jacobs, M.R. Lack of effect of oral sulforaphane administration on NRF2 expression in COPD: a randomized, double-blind, placebo controlled trial. PLoS One,  2016, 11(11)e0163716
[http://dx.doi.org/10.1371/journal.pone.0163716] [PMID: 27832073] 
[73] 
Boehm, J.; Davis, R.; Murar, C.E.; Li, T.; McCleland, B.; Dong, S.; Yan, H.; Kerns, J.; Moody, C.J.; Wilson, A.J.; Graves, A.P.; Mentzer, M.; Qi, H.; Yonchuk, J.; Kou, J.P.; Foley, J.; Sanchez, Y.; Podolin, P.L.; Bolognese, B.; Booth-Genthe, C.; Galop, M.; Wolfe, L.; Carr, R.; Callahan, J.F. Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo. Bioorg. Med. Chem.,  2019, 27(4), 579-588.
[http://dx.doi.org/10.1016/j.bmc.2018.12.026] [PMID: 30626555] 
[74] 
Wang, T.; Dai, F.; Li, G-H.; Chen, X-M.; Li, Y.R.; Wang, S.-Q.; Ren, D-M.; Wang, X-N.; Lou, H-X.; Zhou, B.; Shen, T. Trans -4,4′-dihydroxystilbene ameliorates cigarette smoke-induced progression of chronic obstructive pulmonary disease via inhibiting oxidative stress and inflammatory response. Free Radic. Biol. Med.,  2019, 152, 525-539.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.11.026] 
[75] 
Yonchuk, J.G.; Foley, J.P.; Bolognese, B.J.; Logan, G.; Wixted, W.E.; Kou, J.P.; Chalupowicz, D.G.; Feldser, H.G.; Sanchez, Y.; Nie, H.; Callahan, J.F.; Kerns, J.K.; Podolin, P.L. Characterization of the potent, selective Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2h-chromen-2-one, in cellular and in vivo models of pulmonary oxidative stress. J. Pharmacol. Exp. Ther.,  2017, 363(1), 114-125.
[http://dx.doi.org/10.1124/jpet.117.241794] [PMID: 28790194] 
[76] 
Rogliani, P.; Matera, M.G.; Page, C.; Puxeddu, E.; Cazzola, M.; Calzetta, L. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir. Res.,  2019, 20(1), 104.
[http://dx.doi.org/10.1186/s12931-019-1078-y] [PMID: 31133026] 
[77] 
Lewandowski, Ł.; Kepinska, M.; Milnerowicz, H. The copper-zinc superoxide dismutase activity in selected diseases. Eur. J. Clin. Invest.,  2019, 49(1)e13036
[http://dx.doi.org/10.1111/eci.13036] [PMID: 30316201] 
[78] 
Lakhdar, R.; Denden, S.; Kassab, A.; Leban, N.; Knani, J.; Lefranc, G.; Miled, A.; Chibani, J.B.; Khelil, A.H. Update in chronic ob-structive pulmonary disease: role of antioxidant and metabolizing gene polymorphisms. Exp. Lung Res.,  2011, 37(6), 364-375.
[http://dx.doi.org/10.3109/01902148.2011.580416] [PMID: 21721950] 
[79] 
Oostwoud, L.C.; Gunasinghe, P.; Seow, H.J.; Ye, J.M.; Selemidis, S.; Bozinovski, S.; Vlahos, R. Apocynin and ebselen reduce influ-enza A virus-induced lung inflammation in cigarette smoke-exposed mice. Sci. Rep.,  2016, 6, 20983.
[http://dx.doi.org/10.1038/srep20983] [PMID: 26877172] 
[80] 
Vlahos, R.; Bozinovski, S. Glutathione peroxidase-1 as a novel therapeutic target for COPD. Redox Rep.,  2013, 18(4), 142-149.
[http://dx.doi.org/10.1179/1351000213Y.0000000053] [PMID: 23849338] 
[81] 
Hollins, F.; Sutcliffe, A.; Gomez, E.; Berair, R.; Russell, R.; Szyndralewiez, C.; Saunders, R.; Brightling, C. Airway smooth muscle NOX4 is upregulated and modulates ROS generation in COPD. Respir. Res.,  2016, 17(1), 84.
[http://dx.doi.org/10.1186/s12931-016-0403-y] [PMID: 27435477] 
[82] 
Hsu, P.S.; Lin, C.M.; Chang, J.F.; Wu, C.S.; Sia, K.C.; Lee, I.T.; Huang, K.Y.; Lin, W.N. Participation of NADPH oxidase-related reactive oxygen species in leptin-promoted pulmonary inflammation: regulation of cPLA2α and COX-2 expression. Int. J. Mol. Sci.,  2019, 20(5), 1078.
[http://dx.doi.org/10.3390/ijms20051078] [PMID: 30832310] 
[83] 
Churg, A.; Marshall, C.V.; Sin, D.D.; Bolton, S.; Zhou, S.; Thain, K.; Cadogan, E.B.; Maltby, J.; Soars, M.G.; Mallinder, P.R.; Wright, J.L. Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.,  2012, 185(1), 34-43.
[http://dx.doi.org/10.1164/rccm.201103-0468OC] [PMID: 21997333] 
[84] 
Kutter, D.; Devaquet, P.; Vanderstocken, G.; Paulus, J.M.; Marchal, V.; Gothot, A. Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit? Acta Haematol.,  2000, 104(1), 10-15.
[http://dx.doi.org/10.1159/000041062] [PMID: 11111115] 
[85] 
Kaluza, J.; Larsson, S.C.; Orsini, N.; Linden, A.; Wolk, A. Fruit and vegetable consumption and risk of COPD: a prospective cohort study of men. Thorax,  2017, 72(6), 500-509.
[http://dx.doi.org/10.1136/thoraxjnl-2015-207851] [PMID: 28228486] 
[86] 
Agler, A.H.; Kurth, T.; Gaziano, J.M.; Buring, J.E.; Cassano, P.A. Randomised vitamin E supplementation and risk of chronic lung disease in the Women’s Health Study. Thorax,  2011, 66(4), 320-325.
[http://dx.doi.org/10.1136/thx.2010.155028] [PMID: 21257986] 
[87] 
Dua, K.; Malyla, V.; Singhvi, G.; Wadhwa, R.; Krishna, R.V.; Shukla, S.D.; Shastri, M.D.; Chellappan, D.K.; Maurya, P.K.; Satija, S.; Mehta, M.; Gulati, M.; Hansbro, N.; Collet, T.; Awasthi, R.; Gupta, G.; Hsu, A.; Hansbro, P.M. Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems. Chem. Biol. Interact.,  2019, 299, 168-178.
[http://dx.doi.org/10.1016/j.cbi.2018.12.009] [PMID: 30553721] 

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DOI https://dx.doi.org/10.2174/0929867327666200604165451	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

Current Medicinal Chemistry

Oxidative and Nitrosative Stress in the Pathogenesis of Obstructive Lung Diseases of Increasing Severity

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