Role of oxidants/antioxidants in smoking-induced lung diseases

Free Radical Biology and Medicine

Volumn 21, Issue 5, 1996, Pages 669-681

  Rahman, Irfan ^a   MacNee, William ^a,b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b ROYAL INFIRMARY OF EDINBURGH   (United Kingdom)

Author keywords

Airway epithelium; Antioxidants; Chronic obstructive pulmonary disease; Free radicals; Neutrophils; Oxidants; Smoking

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; BETA CAROTENE; CYSTEINE; DEFEROXAMINE; GLUTATHIONE; LIPID PEROXIDE; OXIDIZING AGENT; PROTEINASE; PROTEINASE INHIBITOR; REACTIVE OXYGEN METABOLITE; SELENIUM; SUPEROXIDE DISMUTASE; THIOL DERIVATIVE;

CHRONIC OBSTRUCTIVE LUNG DISEASE; CIGARETTE SMOKING; CLINICAL TRIAL; HUMAN; HUMAN CELL; INFLAMMATION; LEUKOCYTE ACTIVATION; LUNG EMPHYSEMA; LUNG INJURY; ORAL DRUG ADMINISTRATION; OXIDATIVE STRESS; PHAGOCYTE; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; REVIEW;

EID: 0029740875     PISSN: 08915849     EISSN: None     Source Type: Journal    
DOI: 10.1016/0891-5849(96)00155-4     Document Type: Article

References (155)

1. 1. Taylor, J. C.; Madison, R.; Kosinska, D. Is antioxidant deficiency related to chronic obstructive disease? Am. Rev. Respir. Dis. 134:285-289; 1986.
2. 2. Church, T.; Pryor, W. A. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect. 64:111-126; 1985.
3. 3. Bluhm, A. C.; Weistein, J.; Sonsa, J. A. Free radicals in tobacco smoke. Nature 229:500; 1971.
4. 4. Forbes, W. F.; Robinson, J. C.; Wright, G. F. Free radicals of biological interests. 1. Electron spin resonance spectra of tobacco smoke condensates. Can. J. Biochem. 5:1087-1098; 1967.
5. 5. Pryor, W. A. Biological effects of cigarette smoke, wood smoke, and the smoke from plastics: The use of electron spin resonance. Free Radic. Biol. Med. 13:659-676; 1992.
6. 6. Pryor, W. A.; Stone, K. Oxidants in cigarette smoke: Radicals, hydrogen peroxides, peroxynitrate, and peroxynitrite. Ann. NY Acad. Sci. 686:12-28; 1993.
7. 7. Pryor, W. A.; Church, D. F.; Evans, M. D.; Rice, W. Y., Jr.; Hayes, J. R. A comparison of the free radical chemistry of tobacco burning cigarettes and cigarettes that only heat tobacco. Free Radic. Biol Med. 8:275-279; 1990.
8. 8. Zang, L. Y.; Stone, K.; Pryor, W. A. Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free. Radic. Biol. Med. 19:161-167; 1995.
9. 9. Buckeley, R. D.; Hackney, J. D.; Clark, K.; Posin, C. Ozone and human blood. Arch. Environ. Health 30:40-43; 1975.
10. 10. Cross, C. E.; Van der Vliet, A.; O'Neill, C. A.; Eiserich, J. P. Reactive oxygen species and the lung. Lancet 343:930-933; 1994.
11. 11. Sies, H. ed. Oxidative stress: Oxidants and antioxidants. London: Academic Press; 1991.
12. 12. Padmaja, S.; Huie, R. E. The reaction of nitric oxide with organic peroxyl radicals. Biochem. Biophys. Res. Commun. 195:539-544; 1993.
13. 13. Janoff, A.; Pryor, W. A.; Bengali, Z. H. Effects of tobacco smoke components on cellular and biochemical processes in the lungs. Am. Rev. Respir. Dis. 136:1058-1064; 1987.
14. 14. Lapenna, D.; Gioia, S. D.; Mezzetti, A.; Ciofani, G.; Consoli, A.; Marzio, L.; Cuccurullo, F. Cigarette smoke, ferritin, and lipid peroxidation. Am. J. Respir. Crit. Care Med. 151:431-435; 1995.
15. 15. Nakayama, T.; Church, D. F.; Pryor, W. A. Quantitative analysis of the hydrogen peroxide formed in aqueous cigarette tar extracts. Free Radic. Biol. Med. 7:9-15; 1989.
16. 16. Kilburn, K.; McKenzie, W. Leucocyte recruitment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor. Science 189:634-637; 1975.
17. 17. Hunninghake, G. W.; Crystal, R. G. Cigarette smoking and lung destruction: Accumulation of neutrophils in the lungs of cigarette smokers. Am. Rev Respir. Dis. 128:833-838; 1983.
18. 18. Schaberg, T.; Haller, H.; Rau, M.; Kaiser, D.; Fassbender, M.; Lode, H. Superoxide anion release induced by platelet-activating factor is increased in human alveolar macrophages from smokers. Eur. Respir. J. 5:387-393; 1992.
19. 19. Richards, G. A.; Therson, A. J.; Carel, A.; Merwe, V. D.; Anderson, R. Spirometric abnormalities in young smokers correlate with increased chemiluminescence responses of activated blood phagocytes. Am. Rev. Respir. Dis. 139:181-187; 1989.
20. 20. Davis, W. B.; Pacht, E. R.; Spatafora, M.; Marin, W. J. II. Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers. J. Lab. Clin. Med. 111:293-298; 1988.
21. 21. Ludwig, P. W.; Hoidal, J. R. Alterations in leucocyte oxidative metabolism in cigarette smokers. Am. Rev. Respir. Dis. 126:977-980; 1982.
22. 22. Hoidal, J. R.; Fox, R. B.; LeMarbe, P. A.; Perri, R.; Repine, J. E. Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers. Am. Rev. Respir. Dis. 123:85-89; 1981.
23. 23. Bridges, R. B.; Fu, M. C; Rehm, S. R. Increased neutrophil myeloperoxidase activity associated with cigarette smoking. Eur. J. Respir. Dis. 67:84-93; 1985.
24. 24. Van Antwerpen, V. L.; Theron, A. J.; Richards, G. A.; Steenkamp, K. J.; Van der Merwe, C. A.; Van der Walt, R.; Anderson, R. Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers. Free Radic. Biol. Med. 18:935-943; 1995.
25. 25. MacNee, W.; Wiggs, B.; Berzberg, A. S.; Hogg, J. C. The effects of cigarette smoking on neutrophil kinetics in human lungs. N. Engl. J. Med. 321:924-928; 1989.
26. 26. Drost, E. M.; Selby, C.; Lannan, S.; Lowe, G. D. O.; MacNee, W. Changes in neutrophil deformability following in vitro smoke exposure: Mechanism and protection. Am. J. Respir. Cell. Mol. Biol. 6:287-295; 1992.
27. 27. Brown, D.; Brown, G.; Williams, J. H.; MacNee, W. Priming of neutrophils sequestered in the pulmonary vasculature in acute alveolitis. Am. Rev. Respir. Dis. 144:668; 1993.
28. 28. Andersen, R.; Theron, A. J.; Richards, G. A.; Myers, M. S.; Rensburg, A. J. V. Passive smoking by human sensitizes circulating neutrophils. Am. Rev. Respir. Dis. 144:570-574; 1991.
29. 29. Carp, H.; Janoff, A. Inactivation of bronchial mucous proteinase inhibitor by cigarette smoke and phagocyte-derived oxidants. Exp. Lung. Res. 1:225-237; 1980.
30. 30. Hubbard, R. C.; Ogushi, F.; Fels, G. A.; Cantin, A. M.; Courtney, M.; Crystal, R. G. Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha-1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase. J. Clin. Invest. 80:1289-1295; 1987.
31. 31. Carp, H.; Miller, F.; Hoidal, J. R.; Janoff, A. Potential mechanisms of emphysema: Alpha 1-protease inhibitor recovered from lungs of cigarette smokers contains oxidised methione and has decreased elastase inhibitory capability. Proc. Natl. Acad. Sci. USA 79:2041-2045; 1982.
32. 32. Kramps, J. A.; Rudolphus, A.; Stolk, J.; Willems, L. N. A.; Dijkman, J. H. Role of antileukoprotease in the lung. Ann. NY Acad. Sci. USA 624:97-108; 1991.
33. 33. Kramps, J. A.; van Twisk, C.; Dijkman, D. H. Oxidative inactivation of antileukoprotease is triggered by polymorphonuclear leucocytes. Clin. Sci. 75:53-62; 1988.
34. 34. Cantin, A.; Crystal, R. G. Oxidants, antioxidants and the pathogenesis of emphysema. Eur. J. Respir. Dis. 66(Suppl 139):7-17; 1985.
35. 35. Laurent, P.; Janoff, A.; Kagan, H. M. Cigarette smoke blocks cross-linking of elastin in vitro. Am. Rev. Respir. Dis. 127:189-192; 1983.
36. 36. Takahashi, H.; Ishidoh, K.; Muno, D.; Ohwada, A.; Nukiwa, T.; Kominami, E.; Kira, S. Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. Am. Rev. Respir. Dis. 147:1562-1568; 1993.
37. 37. Ogushi, F.; Hubbard, R. C.; Fells, G. A.; Crystal, R. G. Risk factors for emphysema: Cigarette smoking is associated with a reduction in the association rate constant of lung alpha 1-antitrypsin for neutrophil elastase. J. Clin. Invest. 87:1060-1065; 1991.
38. 38. Selby, C.; Drost, E.; Wraith, P. K.; MacNee, W. In vivo neutrophil sequestration within lungs of humans is determined by in vitro "filterability". J. Appl. Physiol. 71:1996-2003; 1991.
39. 39. Drost, E. M.; Selby, C.; Bridgeman, M. M. E.; MacNee, W. Decreased leucocyte deformability after acute cigarette smoking in humans. Am. Rev. Respir. Dis. 148:1277-1283; 1993.
40. 40. Shoji, S.; Ertl, R. F.; Koyama, S.; Robbins, R.; Leikauf, G.; Essen, S. V.; Rennard, S. I. Cigarette smoke stimulates release of neutrophil chemotactic activity from cultured bovine bronchial epithelial cells. Clin. Sci. 88:337-344; 1995.
41. 41. Ward, P. A. The chemotaxis system. In: Cohan, R. S.; Kaufman, N. eds. Current topics in inflammation and infection. Baltimore: Williams and Wilkins; 1982:54-61.
42. 42. Brown, D. M.; Drost, E.; Donaldson, K.; MacNee, W. Deformability and CD11/CD18 expression of sequestered neutrophils in normal and inflamed lungs. Am. J. Respir. Cell Mol. Biol. 13:531-539; 1995.
43. 43. Lehr, H. A.; Kress, E.; Menger, M. D.; Friedl, H. P.; Hubner, C.; Arfors, K. E.; Messmer, K. Cigarette smoke elicits leukocyte adhesion to endothelium in hamsters: Inhibition by CuZnSOD. Free. Radic. Biol. Med. 14:573-581; 1993.
44. 44. Klut, M. E.; Doerschuk, C. M.; Hogg, J. C.; Vaneedon, S. F.; Burns, A. R. Activation of neutrophils within pulmonary microvessels of rabbits exposed to cigarette smoke. Am. J. Respir. Cell. Mol. Biol. 9:82-90; 1993.
45. 45. Nathan, C.; Srimal, S.; Farber, C.; Sanchez, E.; Kabbash, L.; Asch, A.; Gailit, J.; Wright, S. Cytokine-induced respiratory burst of human neutrophils; Dependence on extracellular matrix proteins and CD11/CD18 integrins. J. Cell. Biol. 109:1341-1349; 1989.
46. 46. Selby, C.; Drost, E.; Brown, D.; Howie, S.; MacNee, W. Inhibition of neutrophil adherence and movement by acute cigarette smoke exposure. Exp. Lung. Res. 18:813-827; 1992.
47. 47. Cross, C. E.; Van der Vliet, A.; O'Neill, C. A.; Louie, S.; Halliwell, B. Oxidants, antioxidants, and respiratory tract lining fluids. Environ. Health. Perspect. 102((Suppl. 10)):185-191; 1994.
48. 48. Cross, C. E.; Halliwell, B.; Allen, A. Antioxidant protection: A function of tracheobranchial and gastrointestinal mucus. Lancet 1:1328-1330; 1984.
49. 49. Dye, J. A.; Adler, K. B. Effects of cigarette smoke on epithelial cells on the respiratory tract. Thorax 49:825-834; 1994.
50. 50. Jones, J. G.; Lawler, P.; Crawley, J. C. W.; Minty, B. D.; Hulands, G.; Veall, N. Increased alveolar epithelial permeability in cigarette smokers. Lancet 1:66-68; 1980.
51. 51. Lannan, S.; Donaldson, K.; Brown, D.; MacNee, W. Effects of cigarette smoke and its condensates on alveolar cell injury in vitro. Am. J. Physiol. 266:L92-L100; 1994.
52. 52. Li, X. Y.; Donaldson, K.; Rahman, I.; MacNee, W. An investigation of the role of glutathione in the increased epithelial permeability induced by cigarette smoke in vivo and in vitro. Am. J. Respir. Crit. Care. Med. 149:1518-1525; 1994.
53. 53. Li, X. Y.; Rahman, I.; Donaldson, K.; MacNee, W. Mechanisms of cigarette smoke induced increased airspace permeability. Thorax 51:465-471; 1996.
54. 54. Rahman, I.; Li, X. Y.; Donaldson, K.; MacNee, W. Cigarette smoke, glutathione metabolism and epithelial permeability in rat lungs. Biochem. Soc. Trans. 23:235S; 1995.
55. 55. Morrison, D.; Lannan, S.; Langridge, A.; Rahman, I.; MacNee, W. Effect of acute cigarette smoking on epithelial permeability, inflammation and oxidant status in the airspaces of chronic smokers. Thorax 49:1077; 1994.
56. 56. Li, X. Y.; Donaldson, K.; Brown, D.; MacNee, W. The role of tumour necrosis factor in increased airspace epithelial permeability in acute lung inflammation. Am. J. Respir. Cell Mol. Biol. 13:185-195; 1995.
57. 57. Chow, C. K. Cigarette smoking and oxidative damage in the lung. Ann. NY Acad. Sci. USA 686:289-298; 1993.
58. 58. Cantin, A.; Crystal, A. G. Oxidants/antioxidants and the pathogenesis of emphysema. Eur. J. Respir. Med. 66(Suppl. 139):7-17; 1985.
59. 59. Selby, C.; Drost, E.; Lannan, S.; Wraith, P. K.; MacNee, W. Neutrophil retention in the lungs of patients with chronic obstructive pulmonary diseases. Am. Rev. Respir. Dis. 143:1359-1364; 1991.
60. 60. Venge, P.; Rak, S.; Steinholtz, S.; Hakansson, L.; Lindblad, G. Neutrophil function in chronic bronchitis. Eur. Respir. J. 4:536-543; 1991.
61. 61. Linden, M.; Rasmussen, J. B.; Pitulainen, E.; Tunek, A.; Larson, M.; Tegner, H.; Venge, P.; Laitinen, L. A.; Brattsand, R. Airway inflammation in smokers and nonobstructive and obstructive chronic bronchitis. Am. Rev. Respir. Dis. 148:1226-1232; 1993.
62. 62. Renkema, T. E. J.; Postma, D. S.; Noordhoek, J. A.; Shriter, H. J.; Kauffman, H. F. Influence of in vivo prednisolone on increased in vitro Superoxide anion generation by neutrophils in emphysema. Eur. Respir. J. 6:90-95; 1993.
63. 63. Postma, D. S.; Renkema, T. E. J.; Noordhoek, J. A.; Faber, H.; Sluiter, H. J.; Kauffman, H. Association between nonspecific bronchial hyperreactivity and superoxide anion production by polymorphonuclear leukocytes in chronic airflow obstruction. Am. Rev. Respir. Dis. 137:57-61; 1988.
64. 64. Rahman, I.; Morrison, D.; Donaldson, K.; MacNee, W. Systemic oxidative stress in asthma, COPD, and smokers. Am. J. Respir. Crit. Care Med. (in press).
65. 65. Muns, G.; Rubinstein, I.; Bergmann, K. C. Phagocytosis and oxidative bursts of blood phagocytes in chronic obstructive airway disease. Scand. J. Infect. Dis. 27:369-373; 1995.
66. 66. Petruzzelli, S.; Hietanen, E.; Bartsch, H.; Camus, A. M.; Mussi, A.; Angeletti, C. A.; Saracci, R.; Giuntini, C. Pulmonary lipid peroxidation in cigarette smokers and lung patients. Chest 98:930-935; 1990.
67. 67. Bridges, A. B.; Scott, N. A.; Parry, G. J.; Belch, J. J. F. Age, sex, cigarette smoking and indices of free radical activity in healthy humans. Eur. J. Med. 2:205-208; 1993.
68. 68. Duthie, G. G.; Arthur, J. R.; James, W. P. T. Effects of smoking and vitamin E on blood antioxidant status. Am. J. Clin. Nutr. 53:1061S-1063S; 1991.
69. 69. Mazzetti, A.; Lapenna, D.; Pierdomenico, S. D.; Calafiore, A. M.; Costantini, F.; Riario-Sforza, G.; Imbastaro, T.; Neri, M.; Cuccurullo, F. Vitamins E, C and lipid peroxidation in plasma and arterial tissue of smokers and nonsmokers. Atherosclerosis 112:91-99; 1995.
70. 2-isoprostanes) in smokers. N. Engl. J. Med. 332:1198-1203; 1995.
71. 71. Lapenna, D.; Mezzetti, A.; Giola, S. D.; Pierdomenico, S. D.; Daniele, F.; Cuccurullo, F. Plasma copper and lipid peroxidation in cigarette smokers. Free Radic. Biol. Med. 19:849-852; 1995.
72. 72. Miller, N. J.; Rice-Evans, C.; Davies, M. J.; Gopinathan, V.; Milner, A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature babies. Clin. Sci. 84:407-412; 1993.
73. 73. O'Neill, C. A.; Halliwell, B.; Van der Vliet, A.; Davis, P. A.; Packer, L.; Tritschler, H.; Strohman, W. J.; Rieland, T.; Cross, C. E.; Reznick, A. Z. Aldehyde-induced protein modifications in human plasma: Protection by glutathione and dihydrolipoic acid. J. Lab. Clin. Med. 124:359-370; 1994.
74. 74. Reznick, A. Z.; Cross, C. E.; Hu, M. L.; Suzuki, Y. J.; Khwaja, S.; Safadi, A.; Motchnik, P. A.; Packer, L.; Halliwell, B. Modification of plasma proteins by cigarette smoke as measured by protein carbonyls formation. Biochem. J. 286:607-611; 1992.
75. 75. Cross, C. E.; O'Neill, C. A.; Reznick, A. Z.; Hu, M. L.; Marcocci, L.; Packer, L.; Frei, B. Cigarette smoke oxidation of human plasma constitutents. Ann. NY Acad. Sci. USA 686:72-90; 1993.
76. 76. Antwerpen, L. V.; Theron, A. J.; Myer, M. S.; Richards, G. A.; Wolmarans, L.; Booysen, U. Cigarette smoke-mediated oxidant stress, phagocytes, vitamin C, vitamin E and tissue injury. Ann. NY Acad. Sci. 686:53-65; 1993.
77. 77. Pelletier, O. Vitamin C status of cigarette smokers and non-smokers. Am. J. Clin. Nutr. 23:520-528; 1970.
78. 78. Chow, C. K.; Thacker, R.; Bridges, R. B.; Rehin, S. R.; Humble, J.; Turbek, J. Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J. Am. Coll. Nutr. 5:305-312; 1986.
79. 79. Bridges, R. B.; Chow, C. K.; Rehm, S. R. Micronutrients and immune functions in smokers. Ann. NY Acad. Sci. 587:218-231; 1990.
80. 80. Theron, A. J.; Richards, G. A.; Rensburg, A. J.; Van der Merwe, C. A.; Anderson, R. Investigation of the role of phagocytes and antioxidant nutrients in oxidant stress mediated by cigarette smoke. Int. J. Vitam. Nutr. Res. 60:261-266; 1990.
81. 81. Barton, G. M.; Roath, O. S. Leukocytic ascorbic acid in abnormal leukocyte states. Int. J. Vitam. Nutr. Res. 46:271-274; 1976.
82. 82. Hemilla, H.; Roberts, P.; Wikstrom, M. Activated polymorphonuclear leukocytes consume vitamin C. FEBS Lett. 178:25-30; 1984.
83. 83. Toth, K. M; Berger, E. M.; Buhler, C. J.; Repine, J. E. Erythrocytes from cigarette smokers contain more glutathione and catalase and protect endothelial cells from hydrogen peroxide better than do erythrocytes from nonsmokers. Am. Rev. Respir. Dis. 134:281-284; 1986.
84. 84. Frei, B.; Forte, T. M.; Ames, B. N.; Cross, C. E. Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Biochem. J. 277:133-138; 1991.
85. 85. Van der Vliet, A.; Smith, D.; O'Neill, C. A.; Kaur, H.; Darley-Usmar, V.; Cross, C. E.; Halliwell, B. Interactions of peroxynitrite and human plasma and its constitutents: Oxidative damage and antioxidant depletion. Biochem. J. 303:295-301; 1994.
86. 86. Eiserich, J. P.; Vossen, V.; O'Neill, C. A.; Halliwell, B.; Cross, C. E.; Van der Vliet, A. Molecular mechanisms of damage by excess nitrogen oxides: Nitration of tyrosine by gas-phase cigarette smoke. FEBS Lett. 353:53-56; 1994.
87. 87. Haddad, I. Y.; Pataki, G.; Hu, P.; Galliani, C.; Beckman, J. S.; Matalon, S. Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. J. Clin. Invest. 94:2407-2413; 1994.
88. 88. Galdston, M.; Levytska, V.; Schwartz, M. S.; Magnusson, B. Ceruloplasmin: Increased serum concentration and impaired antioxidant activity in cigarette smokers, and ability to prevent suppression of elastase inhibitory capacity of alpha-1-proteinase inhibitor. Am. Rev. Respir. Dis. 129:258-263; 1984.
89. 89. Gaziano, J. M.; Manson, J. E.; Buring, J. E.; Hennekens, C. H. Dietary antioxidants and cardiovascular disease. Ann. NY Acad. Sci. 669:249-259; 1992.
90. 90. Thompson, R. L.; Margett, B. M.; Wood, A.; Jackson, A. A. Cigarette smoking and food and nutrient intakes in relation to coronary heart disease. Nutr. Res. Rev. 5:131-152; 1992.
91. 91. Hoffman, R. M.; Garewal, H. S. Antioxidants and the prevention of coronary heart disease. Arch. Intern. Med. 155:241-246; 1995.
92. 92. Eiserich, J. P.; Van der Vliet, A.; Handelman, G. J.; Halliwell, B.; Cross, C. E. Dietary antioxidants and cigarette smoke-induced biomolecular damage: A complex interaction. Am. J. Clin. Nutr. 62:1490S-1500S; 1995.
93. 93. Harats, D.; Ben-Naim, M.; Dabach, Y.; Hollander, G.; Stein, O.; Stein, Y. Cigarette smoking renders LDL susceptible to peroxidative modification and enhanced metabolism by macrophages. Atherosclerosis 79:245-252; 1989.
94. 94. Kita, T.; Yokode, M.; Arai, H.; Hyama, M.; Ueda, Y.; Yeyama, K.; Nurumiya, S. Cigarette smoke, LDL and cholesteryl ester accumulation in macrophages. Ann. NY Acad. Sci. USA 686:91-98; 1993.
95. 95. Steinberg, D.; Parthasarathy, S.; Carew, T. W.; Khoo, J. C.; Witztum, J. L. Beyond choesterol: Modification of low density lipoprotein that increases it atherogenicity. N. Engl. J. Med. 320:915-924; 1989.
96. 96. Mezzetti, A.; Lapenna, D.; Pierdomenico, S. D.; Calafiore, A. M.; Costantini, F.; Riario-Sforza, G.; Imbastaro, T.; Neri, M.; Cuccurullo, F. The vitamin E, C, and lipid peroxidation in plasma and arterial tissue of smokers and nonsmokers. Atherosclerosis 112:91-99; 1995.
97. 97. Sanderson, K. J.; Van Rij, A. M.; Wade, C. R.; Sutherland, W. H. F. Lipid peroxidation of circulating low density lipoproteins with age, smoking and in peripheral vascular disease. Atherosclerosis 118:45-51; 1995.
98. 98. Cantin, A. M.; Fells, G. A.; Hubbard, R. C.; Crystal, R. G. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract. J. Clin. Invest. 86:962-971; 1990.
99. 99. Cooper, B.; Creeth, J. M.; Donald, A. S. R. Studies of the limited degradation of mucus glycoproteins: The mechanism of the peroxide reaction. Biochem. J. 228:615-626; 1985.
100. 100. Cross, C. E.; Halliwell, B.; Allen, A. Antioxidant protection: A function of tracheobronchial and gastointestinal mucus. Lancet 1:1328-1330; 1984.
101. 101. Hu, M.-L.; Louie, S.; Cross, C. E.; Motchnik, P.; Halliwell, B. Antioxidant protection against hypochlorous acid in human plasma. J. Lab. Clin. Med. 121:257-262; 1993.
102. 102. Gum, J. R. Mucin genes and the proteins they encode: Structure, diversity and regulation. Am. J. Respir. Cell. Mol. Biol. 7:557-564; 1992.
103. 103. Cantin, A. M.; North, S. L.; Hubbard, R. C.; Crystal, R. G. Normal alveolar epithelial lung fluid contains high levels of glutathione. J. Appl. Physiol. 63:152-157; 1987.
104. 104. Linden, M.; Hakansson, L.; Ohlsson, K.; Sjodin, K.; Tegner, A.; Tunek, A.; Venge, P. Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity. Inflammation 13:651-658; 1989.
105. 105. Rahman, I.; Li, X. Y.; Donaldson, K.; Harrison, D. J.; MacNee, W. Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. Am. J. Physiol: Lung Cell Mol. Biol. 269:L285-L292; 1995.
106. 106. Pacht, E. R.; Kaseki, H.; Mohammed, J. R.; Cornwell, D. G.; Davis, W. R. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity. J. Clin. Invest. 77:789-796; 1988.
107. 107. Bui, M. H.; Sauty, A.; Collet, F.; Leuenberger, P. Dietary vitamin C intake and concentrations in the body fluids and cells of male smokers and nonsmokers. J. Nutr. 122:312-336; 1992.
108. 108. McGowan, S. E.; Parenti, C. M.; Hoidal, J. R.; Niewoehner, D. W. Differences in ascorbic acid content and accumulation by alveolar macrophages from cigarette smokers and non-smokers. J. Lab. Clin. Med. 104:127-134; 1984.
109. 109. McCusker, K.; Hoidal, J. Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. Am. Rev. Respir. Dis. 141:678-682; 1990.
110. 110. Kondo, T.; Tagami, S.; Yoshioka, A.; Nishumura, M.; Kawakami, Y. Current smoking of elderly men reduces antioxidants in alveolar macrophages. Am. J. Respir. Crit. Care Med. 149:178-182; 1994.
111. 111. York, G. K.; Pierce, T. H.; Schwartz, L. S.; Cross, C. E. Stimulation by cigarette smoke of glutathione peroxidase system enzyme activities in rat lung. Arch. Environ. Health 31:286-290; 1976.
112. 112. Rahman, I.; Lawson, M.; Smith, C. A. D.; Harrison, D. J.; MacNee, W. Elevation of γ-Glutamylcysteine synthetase gene expression by cigarette smoke exposure in alveolar epithelial cells. Am. J. Respir. Crit. Care Med. 151:A645; 1995.
113. 113. Schulze-Qsthoff, K.; Los, M.; Baeuerle, P. A. Redox signalling by transcription factors NF-kB and AP-1 in lymphocytes. Biochem. Pharmacol. 50:735-741; 1995.
114. 114. Jany, B.; Betz, R.; Schreck, R. Activation of transcription factor NF-kB in human tracheobronchial epithelial cells by inflammatory stimuli. Eur. Respir. J. 8:387-391; 1995.
115. 115. Peristeris, P.; Clark, B. D.; Gatti, S.; Faggioni, R.; Mantovani, A.; Mengozzi, M.; Orencole, S. F.; Sironi, M.; Ghezzi, P. N-Acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. Cell. Immunol. 140:390-399; 1992.
116. 116. Tappia, P. S.; Troughton, K. L.; Langley-Evans, S. C.; Grimble, R. F. Cigarette smoking influences cytokine production and antioxidant defences. Clin. Sci. 88:485-489; 1995.
117. 117. Menkes, M.; Comstock, G.; Vuilleumier, J.; Helsing, K.; Rider, E.; Brookmeyer, R. Serum beta-carotene, vitamins A and E, selenium and the risk of lung cancer. N. Engl. J. Med. 315:1250-1254; 1986.
118. 118. Blot, W.; Li, X. Y.; Taylor, P.; Guo, W.; Dawsey, S.; Wang, G. Q.; Yang, G. S.; Zheng, S. F.; Gail, M.; Li, G. Y.; Yu, Y.; Lin, B.; Tangrea, J.; Sun, Y.; Lin, F.; Fraumeni, J. F.; Zhang, Y. H.; Li, B. Nutrition intervention trials in Linxian China: Supplementation with specific vitamin/mineral combination, cancer incidence and disease-specific mortality in the general population. J. Natl. Cancer. Inst. 85:1483-1492; 1993.
119. 119. Kardinaal, A. F. M.; Kok, F. J.; Rinstad, J.; Gomez-Aracena, J.; Mazaev, V. P.; Kohlmeier, L.; Martin, B. C.; Aro, A.; Kark, J. D.; Delgado-Rodriguez, M.; Riemersma, R. A.; Veer, P. V.; Huttumen, J. K.; Martin-Mareno, J. M. Antioxidants in adipose tissue and risk of myocardial infarction: The EURAMIC study. Lancet 342:1379-1384; 1993.
120. 120. Bucca, C.; Rolla, G.; Arossa, W.; Caria, E.; Elia, C.; Nebiolo, F.; Baldi, S. Effect of ascorbic acid on increased bronchial responsiveness during upper airway function. Respiration 55:214-219; 1989.
121. 121. Schwartz, J.; Weiss, S. T. Relationship between dietary vitamin C intake and pulmonary function in First National Health and Nutrition Examination Survey (NHANES I). Am. J. Clin. Nutr. 59:110-114; 1994.
122. 122. Clausen, J. The influence of antioxidants on the enhanced respiratory burst reaction in smokers. Ann. NY Acad. Sci. 629:337-341; 1991.
123. 123. Hoshino, E.; Shariff, R.; Van Gossum, A. Vitamin E suppresses increased lipid peroxidation in cigarette smokers. J. Parenter. Enter. Nutr. 40:300-305; 1990.
124. 124. Churg, A.; Chrukupalli, K. Cigarette smoke causes rapid lipid peroxidation of rat tracheal epithelium. Int. J. Exp. Pathol. 74:127-132; 1993.
125. 125. Cohen, A. B.; James, H. L. Reduction of the elastase inhibitory capacity of alpha 1-antitrypsin by peroxides in cigarette smoke: An analysis of brands and filters. Am. Rev. Respir. Dis. 126:25-30; 1982.
126. 126. Barnard, M. L.; Baker, R. R.; Matalon, S. Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. Am. J. Physiol. 265:L340-L345; 1993.
127. 127. Heffner, J. E.; Repine, J. E. Pulmonary strategies of antioxidant defence. Am. Rev. Respir. Dis. 140:531-554; 1989.
128. 128. White, C. W.; Jackson, J. H.; Abuchowski, E. Polyethylene glycol-attached antioxidant enzyme decrease pulmonary oxygen toxicity in rats. J. Appl. Physiol. 66:584-590; 1989.
129. 129. Turrens, J. F.; Crapo, J. D.; Freeman, B. A. Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. J. Clin. Invest. 73:87-95; 1984.
130. 130. Flick, M. R.; Milligan, S. A.; Hoeffel, J. M.; Goldstein, I. M. Catalase prevents increased lung vascular permeability during air emboli in unanesthetised sheep. J. Appl. Physiol. 64:929-935; 1988.
131. 131. Flick, M. R.; Hoeffel, J. M.; Staub, N. C. Superoxide dismutase with heparin prevents increased lung vascular permeability during air emboli in sheep. J. Appl. Physiol. 55:1284-1291; 1983.
132. 132. Freeman, B. A.; Yong, S. L; Crapo, J. D. Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury. J. Biol. Chem. 258:12534-12542; 1983.
133. 133. Padmanabhan, R. V.; Guadapaty, I. E.; Lienen, I. E.; Schwartz, B. A.; Hoidal, J. R. Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. Am. Rev. Respir. Dis. 132:164-167; 1985.
134. 134. McDonald, R. J.; Berger, E. M.; White, C. W.; White, J. G.; Freeman, B. A.; Repine, J. E. Effect of superoxide dismutase encapsulated in liposomes or conjugated with polyethylene glycol on neutrophil bactericidal activity in vitro and bacterial clearance in vivo. Am. Rev. Respir. Dis. 131:633-637; 1985.
135. 135. Meister, A.; Anderson, M. E. Glutathione. Annu. Rev. Biochem. 52:711-760; 1983.
136. 136. Meister, A. Selective modification of glutathione metabolism. Science 220:472-477; 1983.
137. 137. Julius, M.; Lang, C. A.; Gleiberman, L.; Harbug, E.; Di-Franceisco, W.; Schork, A. Glutathione and morbidity in a community-based sample of elderly. J. Clin. Epidemiol. 47:1021-1026; 1994.
138. 138. Moldeus, P.; Berggren, M.; Grafstrom, 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. 66(Suppl. 139):123-129; 1985.
139. 139. MacNee, W.; Rahman, I. Oxidants/antioxidants in idiopathic pulmonary fibrosis. Thorax 50(Suppl. 1):S53-S58; 1995.
140. 140. Bridgeman, M. M. E.; Marsden, M.; MacNee, W.; Flenley, D. C.; Ryle, A. P. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax 46:39-42; 1991.
141. 141. Bridgeman, M. M. E.; Marsden, M.; Selby, C.; Morrison, D.; MacNee, W. Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid and lining tissue. Thorax 49:670-675; 1994.
142. 142. Moldeus, P.; Cotgreave, I. A.; Berggren, M. Lung protection by the thiol-containing antioxidant: N-acetylcysteine. Respiration 150(Suppl. 1):31-42; 1986.
143. 143. Olsson, B.; Johansson, M.; Gabrielson, J.; Bolme, P. Pharmacokinetics of reduced and oxidised N-acetylcysteine. Eur. J. Clin. Pharmacol. 34:77-82; 1988.
144. 144. Sheffner, A. L.; Medler, E. M.; Bailey, K. R.; Gallo, D. G.; Mueller, A. J.; Sarett, H. P. Metabolic studies with N-acetyl-cysteine. Biochem. Pharmacol. 15:1523-1535; 1966.
145. 145. Berggren, M.; Dawson, J.; Moldeus, P. Glutathione biosynthesis in the isolated perfused rat lung: Utilisation of extracellular glutathione. FEBS Lett. 176:189-192; 1984.
146. 146. Bonanomi, L.; Gazzaniga, A. Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur. J. Respir. Dis. 61:52-58; 1980.
147. 147. Boman, G.; Backer, U.; Larsson, S.; Melander, B.; Wahlander, L. Oral acetylcysteine reduces exacerbation rate in chronic bonchitis. Eur. J. Respir. Dis. 64:405-415; 1983.
148. 148. Rasmussen, J. B.; Glennow, C. Reduction in days of illness after long term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Eur. J. Respir. Dis. 1:351-355; 1988.
149. 149. British Thoracic Society Research Committee Oral N-acetyl-cysteine and exacerbation rats in patients with chronic bronchitis and severe airways obstruction. Thorax 40:832-835; 1985.
150. 150. Borok, Z.; Buhl, R.; Grimes, G. J.; Bokser, A. D.; Hubbard, R. C.; Holroyd, K. J.; Roum, J. H.; Czerski, D. B.; Cantin, A. M.; Crystal, R. G. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet 338:215-216; 1991.
151. 151. Puri, R. N.; Meister, A. Transport of glutathione, as gamma-glutamyl-cysteinylglycyl ester, into liver and kidney. Proc. Natl. Acad. Sci. USA 80:5258-5260; 1993.
152. 152. Deneke, S. M.; Baxter, D. F.; Phelps, D. T.; Fanburg, B. L. Increase in endothelial cell glutathione and precursor amino acid uptake by diethylmaleate and hyperoxia. Am. J. Physiol. 257:L265-L271; 1989.
153. 153. Williamson, J. M.; Boettcher, B.; Meister, A. Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc. Natl. Acad. Sci. USA 79:6246-6249; 1982.
154. 154. Porta, P.; Aebi, S.; Summer, K.; Lauterburgh, B. H. L-2-Oxothiazolidine-4-carboxylic acid, a cysteine pro drug: Pharmacokinetics and effects on thiols in plasma and lymphocytes in human. J. Pharmacol. Exp. Ther. 257:331-334; 1991.
155. 155. Munday, R. Toxicity of thiols and disulphides: Involvement of free radical species. Free. Radic. Biol. Med. 7:659-673; 1989.