Antioxidant properties of N-acetylcysteine: Their relevance in relation to chronic obstructive pulmonary disease

European Respiratory Journal

Volumn 23, Issue 4, 2004, Pages 629-636

  Dekhuijzen, P N R ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

N Acetylcysteine chronic obstructive pulmonary disease inflammation oxidative stress pathogenesis

Indexed keywords

ACETYLCYSTEINE; ANTIOXIDANT; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; CIGARETTE SMOKE; CORTICOSTEROID DERIVATIVE; DEXAMETHASONE; GLUTATHIONE; MUCOLYTIC AGENT; REACTIVE OXYGEN METABOLITE;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; DISEASE COURSE; DISEASE EXACERBATION; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG COST; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG POTENTIATION; GASTROINTESTINAL SYMPTOM; HUMAN; IMMUNE RESPONSE; INFECTION RISK; INFLAMMATORY CELL; LUNG FUNCTION; LUNG PARENCHYMA; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; RETROSPECTIVE STUDY; REVIEW;

ACETYLCYSTEINE; ANTIOXIDANTS; DISEASE PROGRESSION; FREE RADICAL SCAVENGERS; HUMANS; OXIDATIVE STRESS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; REACTIVE OXYGEN SPECIES;

EID: 1842481121     PISSN: 09031936     EISSN: None     Source Type: Journal    
DOI: 10.1183/09031936.04.00016804     Document Type: Review

References (102)

1. Repine JE, Lankhorst ILM, Debacker WA, et al. Oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156: 341-357.
2. Rahman I, MacNee W. Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease. Am J Physiol 1999; 277: L1067-L1088.
3. MacNee W, Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: S58-S65.
4. MacNee W. Oxidants/antioxidants and COPD. Chest 2000; 117: 5 Suppl. 1, 303S-317S.
5. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000; 343: 269-280.
6. Rahman I, MacNee W. Role of oxidants/antioxidants in smoking-induced lung diseases. Free Radic Biol Med 1996; 21: 669-681.
7. Warren JS, Johnson KJ, Ward PA. Consequences of oxidant injury. In: Crystal RG, West JB, Weibel ER, Barnes PJ, eds. The Lung: Scientific Foundations. New York, NY, Raven Press Ltd, 1997; pp. 2279-2288.
8. Wilkinson TM, Patel IS, Wilks M, Donaldson GC, Wedzicha JA. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003; 167: 1090-1095.
9. MacNee W. Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 2001; 429: 195-207.
10. Morrison D, Rahman I, Lannan S, MacNee W. Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. Am J Respir Crit Care Med 1999; 159: 473-479.
11. Mateos F, Brock JH, Perez-Arellano JL. Iron metabolism in the lower respiratory tract. Thorax 1998; 53: 594-600.
12. Cantin AM, North SL, Hubbard R, Crystal RG. Normal alveolar epitheliaL lining fluid contains high levels of glutathione. J Appl Physiol 1987; 63: 152-157.
13. Rahman I, Morrison D, Donaldson K, MacNee W. Systemic oxidative stress in asthma, COPD, and smokers. Am J Respir Crit Care Med 1996; 154: 1055-1060.
14. Rahman I, Skwarska E, MacNee W. Attenuation of oxidant/ antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease. Thorax 1997; 52: 565-568.
15. Maranzana A, Mehlhorn RJ. Loss of glutathione, ascorbate recycling, and free radical scavenging in human erythrocytes exposed to filtered cigarette smoke. Arch Biochem Biophys 1998; 350: 169-182.
16. Laurent P, Janoff A, Kagan HM. Cigarette smoke blocks cross-linking of elastin in vitro. Am Rev Respir Dis 1983; 127: 189-192.
17. Cantin A, Crystal RG. Oxidants, antioxidants and the pathogenesis of emphysema. Eur J Respir Dis 1985; 66: Suppl. 139, 7-17.
18. Ghezzi P, Dinarello CA, Bianchi M, Rosandich ME, Repine JE, White CW. Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine 1991; 3: 189-194.
19. Metinko AP, Kunkel SL, Standiford TJ, Strieter RM. Anoxia-hyperoxia induces monocyte-derived interleukin-8. J Clin Invest 1992; 90: 791-798.
20. 1-protease inhibitor in bronchoalveolar lavage fluid. Am Rev Respir Dis 1985; 131: 79-85.
21. Maier KL, Leuschel L, Costabel U. Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis. Eur Respir J 1992; 5: 651-658.
22. Cotgreave IA, Moldeus P. Lung protection by thiol-containing antioxidants. Bull Eur Physiopathol Respir 1987; 23: 275-277.
23. MacNee W, Wiggs B, Belzberg AS, Hogg JC. The effect of cigarette smoking on neutrophil kinetics in human lungs. N Engl J Med 1989; 321: 924-928.
24. Rahman I, MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J 2000; 16: 534-554.
25. Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS, on behalf of the GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/ WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001; 163: 1256-1276.
26. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: 1635-1639.
27. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med 1997; 155: 542-548.
28. Culpitt SV, Rogers DF, Shah P, et al. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003; 167: 24-31.
29. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996; 156: 4422-4428.
30. Confalonieri M, Mainardi E, Della PR, et al. Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease. Thorax 1998; 53: 583-585.
31. Thompson AB, Mueller MB, Heires AJ, et al. Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation. Am Rev Respir Dis 1992; 146: 389-395.
32. Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: A double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002; 165: 1592-1596.
33. Ferreira IM, Hazari MS, Gutierrez C, Zamel N, Chapman KR. Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: Effects of inhaled beclomethasone. Am J Respir Crit Care Med 2001; 164: 1012-1015.
34. van Beurden WJC, Harff GA, Dekhuijzen PNR, van der Poel-Smet SM, Smeenk FWJM. Effects of inhaled corticosteroids with different lung deposition on exhaled hydrogen peroxide in stable COPD patients. Respiration 2003; 70: 242-248.
35. Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med 1999; 340: 1948-1953.
36. Vestbo J, Sorensen T, Lange P, Brix A, Torre P, Viskum K. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: A randomised controlled trial. Lancet 1999; 353: 1819-1823.
37. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: The ISOLDE trial. BMJ 2000; 320: 1297-1303.
38. Lung Health Study Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000; 343: 1902-1909.
39. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002; 166: 1084-1091.
40. Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003; 21: 74-81.
41. Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22: 912-919.
42. 2 agonists study group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial. Lancet 2003; 361: 449-456.
43. Moldeus P, Cotgreave IA, Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986; 50: 31-42.
44. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 1989; 6: 593-597.
45. Cotgreave IA. N-acetylcysteine: Pharmacological considerations and experimental and clinical applications. Adv Pharmacol 1997; 38: 205-227.
46. Sheffner AL, Medler EM, Bailey KR, Gallo DG, Mueller AJ, Sarett HP. Metabolic studies with acetylcysteine. Biochem Pharmacol 1966; 15: 1523-1535.
47. Rodenstein D, DeCoster A, Gazzaniga A. Pharmacokinetics of oral acetylcysteine: Absorption, binding and metabolism in patients with respiratory disorders. Clin Pharmacokinet 1978; 3: 247-254.
48. Borgstrom L, Kagedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986; 31: 217-222.
49. Cotgreave IA, Eklund A, Larsson K, Moldeus P. No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid. Eur J Respir Dis 1987; 70: 73-77.
50. Bridgeman MM, Marsden M, MacNee W, Flenley DC, Ryle AP. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax 1991; 46: 39-42.
51. Bridgeman MM, Marsden M, Selby C, Morrison D, MacNee W. Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue. Thorax 1994; 49: 670-675.
52. Schreck R, Albermann K, Baeuerle PA. Nuclear factor κB: An oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun 1992; 17: 221-237.
53. Bridges RB. Protective action of thiols on neutrophil function. Eur J Respir Dis 1985; 66: Suppl. 139, 40-48.
54. Voisin C, Aerts C, Wallaert B. Prevention of in vitro oxidant-mediated alveolar macrophage injury by cellular glutathione and precursors. Bull Eur Physiopathol Respir 1987; 23: 309-313.
55. Linden M, Wieslander E, Eklund A, Larsson K, Brattsand R. Effects of oral N-acetylcysteine on cell content and macrophage function in bronchoalveolar lavage from healthy smokers. Eur Respir J 1988; 1: 645-650.
56. Moldeus P, Berggren M, Graffström R. N-Acetylcysteine protection against the toxicity of cigarette smoke and cigarette smoke condensates in various tissues and cells in vitro. Eur J Respir Dis 1985; 66: Suppl. 139, 123-129.
57. Drost E, Lannan S, Bridgeman MME, et al. Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. Eur Respir J 1991; 4: 723-729.
58. Jeffery PK, Rogers DF, Ayers MM. Effect of oral acetylcysteine on tobacco smoke-induced secretory cell hyperplasia. Eur J Respir Dis 1985; 66: Suppl. 139, 117-122.
59. 1-proteinase inhibitor by N-acetyl cysteine, glutathione, and methionine. Agents Actions 1987; 22: 255-260.
60. Rubio ML, Sanchez-Cifuentes MV, Ortega M, et al. N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur Respir J 2000; 15: 505-511.
61. Santini MT, Straface E, Cipri A, Peverini M, Santulli M, Malorni W. Structural alterations in erythrocytes from patients with chronic obstructive pulmonary disease. Haemostasis 1997; 27: 201-210.
62. Cuzzocrea S, Mazzon E, Dugo L, et al. Protective effects of N-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat. FASEB J 2001; 15: 1187-1200.
63. Schmid G, Li Bianchi E, Straface E, et al. N-acetylcysteine (NAC) counteracts erythrocyte damage and is useful in the management of COPD. Am J Respir Crit Care Med 2002; 165: A227.
64. Jankowska R, Passowicz-Muszynska E, Medrala W, Banas T, Marcinkowska A. The influence of N-acetylcysteine on chemiluminescence of granulocytes in peripheral blood of patients with chronic bronchitis. Pneumonol Alergol Pol 1993; 61: 586-591.
65. De Backer W, van Overveld F, Vandekerckhove K. Sputum ECP levels in COPD patients decrease after treatment with N-acetylcysteine (NAC). Eur Respir J 1997; 12: 225s.
66. Riise GC, Qvarfordt I, Larsson S, Eliasson V, Andersson BA. Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration 2000; 67: 552-558.
67. Bergstrand H, Björnson A, Eklund A, et al. Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: Modulation by N-acetylcysteine treatment in vivo. J Free Radic Biol Med 1986; 2: 119-127.
68. Eklund A, Eriksson O, Hakansson L, et al. Oral N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: Correlation to effects on cellular variables. Eur Respir J 1988; 1: 832-838.
69. Marui N, Offermann MK, Swerlick R, et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 1993; 92: 1866-1874.
70. Streightoff F, Redman CE, DeLong DC. In vivo antiviral chemotherapy. II. Anti-influenza action of compounds affecting mucous secretions. Antimicrobial Agents Chemother 1966; 6: 503-508.
71. Knobil K, Choi AM, Weigand GW, Jacoby DB. Role of oxidants in influenza virus-induced gene expression. Am J Physiol 1998; 274: L134-L142.
72. - generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J Clin Invest 1990; 85: 739-745.
73. Biagioli MC, Kaul P, Singh I, Turner RB. The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells. Free Radic Biol Med 1999; 26: 454-462.
74. Dekhuijzen PNR, Aben KKH, Dekker I, et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable COPD. Am J Respir Crit Care Med 1996; 154: 813-816.
75. Kasielski M, Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med 2001; 95: 448-456.
76. De Benedetto F, Aceto A, Formisano S, et al. Long-term treatment with N-acetylcysteine (NAC) decreases hydrogen peroxide level in exhaled air of patients with moderate COPD. Am J Respir Crit Care Med 2001; 163: A725.
77. Braga PC, Allegra L. Drugs in Bronchial Mucology. New York, NY, Raven Press, 1989; pp. 77-102.
78. Nightingale JA, Rogers DF. Should drugs affecting Mucus properties be used in COPD? Clinical evidence. In: Similowski T, Whitelaw WA, Derenne JP, eds. Clinical Management of Chronic Obstructive Pulmonary Disease. New York, NY, Basle, Marcel Dekker, Inc., 2002; pp. 405-425.
79. Sheffner AL, Medler EM, Jacobs LW, Sarett HP. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am Rev Respir Dis 1964; 90: 721-729.
80. Martin R, Litt M, Marriott C. The effect of mucolytic agents on the rheologic and transport properties of canine tracheal mucus. Am Rev Respir Dis 1980; 121: 495-500.
81. Rogers DF, Jeffery PK. Inhibition by oral N-acetylcysteine of cigareIte smoke-induced "bRonchitis" in the rat. Exp Lung Res 1986; 10: 267-283.
82. Rogers DF, Turner NC, Marriott C, Jeffery PK. Oral N-acetylcysteine or S-carboxymethylcysteine inhibit cigarette smoke-induced hypersecretion of mucus in rat larynx and trachea in situ. Eur Respir J 1989; 2: 955-960.
83. Rogers DF, Godfrey RW, Majumdar S, Jeffery PK. Oral N-acetylcysteine speeds reversal of cigarette smoke-induced mucous cell hyperplasia in the rat. Exp Lung Res 1988; 14: 19-35.
84. Tattersall AB, Bridgman KM, Huitson A. Acetylcysteine (Fabrol) in chronic bronchitis - a study in general practice. J Int Med Res 1983; 11: 279-284.
85. Multicenter Study Group. Long-term oral acetylcysteine in chronic bronchitis. A double-blind controlled study. Eur J Respir Dis 1980; 61: Suppl. 111, 93-108.
86. Riise GC, Larsson S, Larsson P, Jeansson S, Andersson BA. The intrabronchial microbial flora in chronic bronchitis patients: A target for N-acetylcysteine therapy? Eur Respir J 1994; 7: 94-101.
87. De Flora S, Grassi C, Carati L. Attenuation of influenza symptomatology and improvement of immunological parameters due to long-term treatment with N-acetylcysteine. Eur Respir J 1997; 10: 1535-1541.
88. Lundbäck B, Lindström M, Andersson S, Nyström L, Rosenhall L, Stjernberg N. Possible effect of acetylcysteine on lung function. Eur Respir J 1992; 5: Suppl. 15, 289s.
89. 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 2000; 16: 253-262.
90. Grassi C, Morandini GC. A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. Eur J Clin Pharmacol 1976; 9: 393-396.
91. Aylward M, Maddock J, Dewland P. Clinical evaluation of acetylcysteine in the treatment of patients with chronic obstructive bronchitis: A balanced double-blind trial with placebo control. Eur J Respir Dis 1980; 61: Suppl. 111, 81-89.
92. Boman G, Backer U, Larsson S, Melander B, Wahlander L. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: Report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983; 64: 405-415.
93. Borgia M, Sepe N, Ori-Belometti M, Borgia M. Confronto tra acetilcisteina e placebo nel trattamento a lungo termine della bronchite cronica. Gaz Med It 1981; 140: 467-472.
94. British Thoracic Society Research Committee. Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitis and severe airways obstruction. Thorax 1985; 40: 832-835.
95. Meister R. Langzeittherapie mit Acetylcystein Retard-Tabletten bei Patienten mit chronischer Bronchitis. Eine doppelblinde-placebokontrollierte Studie. Forum Prakt Allg Artz 1986; 25: 18-22.
96. Parr GD, Huitson A. Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. Br J Dis Chest 1987; 81: 341-348.
97. Rasmussen JB, Glennon C. Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Eur Respir J 1988; 1: 351-355.
98. Hansen NCG, Skriver A, Brorsen-Riis L, et al. Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Respir Med 1994; 88: 531-535.
99. Jackson IM, Barnes J, Cooksey P. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: A double-blind placebo controlled study. J Int Med Res 1984; 12: 198-206.
100. 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 2000; 22: 209-221.
101. Poole PJ, Black PN. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: Systematic review. BMJ 2001; 322: 1271-1274.
102. Decramer M, Dekhuijzen PNR, Troosters T, et al. The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): Hypothesis and design. BRONCUS-trial Committee. Eur Respir J 2001; 17: 329-336.