Prevalence of asthma has increased considerably in recent decades throughout the world especially in developed countries. Airway inflammation is thought to be prime cause for repeated episodes of airway obstruction in asthmatics. Several studies have shown that reactive oxygen species (ROS) play a key role in initiation as well as amplification of inflammation in asthmatic airways. Excessive ROS production in asthma leads to alteration in key enzymatic as well as nonenzymatic antioxidants such as glutathione, vitamins C and E, beta-carotene, uric acid, thioredoxin, superoxide dismutases, catalase, and glutathione peroxidases leading to oxidant—antioxidant imbalance in airways. Oxidant—antioxidant imbalance leads to pathophysiological effects associated with asthma such as vascular permeability, mucus hypersecretion, smooth muscle contraction, and epithelial shedding. Epidemiological data also support the scientific evidence of oxidant—antioxidant imbalance in asthmatics. Therefore, the supplementation of antioxidants to boost the endogenous antioxidants or scavenge excessive ROS production could be utilized to dampen/prevent the inflammatory response in asthma by restoring oxidant—antioxidant balance. This review summarizes the scientific and epidemiological evidence linking asthma with oxidant—antioxidant imbalance and possible antioxidant strategies that can be used therapeutically for better management of asthma.
Aderele, W.I., Ojo, C., Osanyintuyi, V.O. and Oduwole, O. (1985) Serum alpha 1-antitrypsin levels in asthmatic children . Afr J Med Med Sci14: 161-167.
2.
Aldridge, R., Chan, T., van Dalen, C., Senthilmohan, R., Winn, M., Venge, P. et al. (2002) Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics. Free Radic Biol Med33: 847-856.
3.
Al-Obaidy, A.H. and Al-Samarai, A.G. (2007) Exhaled breath condensate pH and hydrogen peroxide as non-invasive markers for asthma. Saudi Med J28: 1860-1863.
4.
Andreadis, A.A., Hazen, S.L., Comhair, S.A. and Erzurum, S.C. (2003) Oxidative and nitrosative events in asthma. Free Radic Biol Med35: 213-225.
5.
Antonicelli, F., Brown, D., Parmentier, M., Drost, E.M., Hirani, N., Rahman, I. et al. (2004) Regulation of LPS-mediated inflammation in vivo and in vitro by the thiol antioxidant nacystelyn. Am J Physiol Lung Cell Mol Physiol286: 1319-1327.
6.
Antonicelli, F., Parmentier, M., Drost, E.M., Hirani, N., Rahman, I., Donaldson, K. et al. (2002) Nacystelyn inhibits oxidant-mediated interleukin-8 expression and NF-kappaB nuclear binding in alveolar epithelial cells. Free Radic Biol Med32: 492-502.
7.
App, E.M., Baran, D., Dab, I., Malfroot, A., Coffiner, M., Vanderbist, F. et al. (2002) Dose-finding and 24-h monitoring for efficacy and safety of aerosolized nacystelyn in cystic fibrosis. Eur Respir J19: 294-302.
8.
Arthur, J. (2000) The glutathione peroxidases. Cell Mol Life Sci57: 1825-1835.
9.
Arts, I.C. and Hollman, P.C. (2005) Polyphenols and disease risk in epidemiologic studies . Am J Clin Nutr81: 317S-325S.
10.
Aruoma, O.I., Whiteman, M., England, T.G. and Halliwell, B. (1997) Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. Biochem Biophys Res Commun231: 389-391.
11.
Avissar, N., Finkelstein, J.N., Horowitz, S., Willey, J.C., Coy, E., Frampton, M.W. et al. (1996) Extracellular glutathione peroxidase in human lung epithelial lining fluid and in lung cells. Am J Physiol270: 173-182.
12.
Azzi, A.P. and Stocker, A. (2000) Vitamin E: non-antioxidant roles. Prog Lipid Res39: 231-255.
13.
Babior, B.M. (1999) NADPH oxidase: an update. Blood93: 1464-1476.
14.
Baraldi, E., Carraro, S., Alinovi, R., Pesci, A., Ghiro, L. et al. (2003) Cysteinyl leukotrienes and 8-isoprostanes in exhaled breath condensate of children with asthma exacerbations. Thorax58: 505-509.
15.
Barnes, P.J. and Drazen, J.M. (2002) Pathophysilogy of asthma. In Barnes, P.J.,Drazen, J.M.,Rennard, S. et al. (eds) Asthma and COPD. London: Academin Press, 343-359.
16.
Barnes, P.J., Chung, K.F. and Page, C.P. (1998) Inflammatory mediators of asthma: an update. Pharmacol Rev50: 515-596.
17.
Barnes, PJ (1994) Cytokines as mediators of chronic asthma. Am J Respir Crit Care Med150: 42-49.
18.
Bibi, H., Schleisnger, M., Tabacnik, E., Schwartz, Y., Iscovitz, H. and Iaina, A. (1988) Erythrocyte glutathione peroxidase activity in asthmatic children. Ann Allergy61: 339-340.
19.
Birrell, M.A., McCluskie, K., Wong, S., Donnelly, L.E., Barnes, P.J. and Belvisi, M.G. (2005) Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism. FASEB J19: 840-841.
20.
Bodner, C., Godden, D., Little, J., Ross, S., Brown, K. and Seaton, A. (1999) Antioxidant intake and adult-onset wheeze: a case-control study. Eur Respir J13: 22-30.
21.
Borok, Z., Buhl, R., Grimes, G.J., Bokser, A.D., Hubbard, R.C., Holroyd, K.J. et al. (1991) Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis, Lancet338: 215-216.
22.
Brennan, M.L., Wu, W., Fu, X., Shen, Z., Song, W., Frost, H. et al. (2002) A tale of two controversies defining both the role of peroxidases in nitrotyrosine formation in vivo using eosinophil peroxidase and myeloperoxidase-deficient mice, and the nature of peroxidase-generated reactive nitrogen species. J Biol Chem277: 17415-17427.
23.
Brigelius-Flohe, R., Aumann, K.D., Blocker, H., Gross, G., Kiess, M., Klöppel, K.D. et al. (1994) Phospholipid- hydroperoxide, glutathione peroxidase, Genomic DNA, cDNA and deduced amino acid sequence. J Biol Chem269: 7342-7348.
24.
Brigelius-Flohe, R. and Traber, M.G. (1999) Vitamin E: function and metabolism. FASEB J13: 1145-1155.
25.
Britton, J.R., Pavord, I.D., Richards, K.A., Knox, A.J., Wisniewski, A.F., Lewis, S.A. et al. (1995) Dietary antioxidants on lung function in the general population. Am J Respir Crit Care Med151: 1383-1387.
26.
Butland, B.K., Fehily, A.M. and Elwood, P.C. (2000) Diet, lung function and lung function decline in a cohort of 2512 middle aged men. Thorax55: 102-108.
27.
Chance, B., Sies, H. and Boveris, A. (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev59: 527-605.
28.
Chang, L.Y. and Crapo, J.D. (2002) Inhibition of airway inflammation and hyperreactivity by an antioxidant mimetic. Free Radic Biol Med33: 379-386.
29.
Chatterjee, P.K., Patel, N.S., Kvale, E.O., Brown, P.A., Stewart, K.N., Mota-Filipe, H. et al. (2004) EUK-134 reduces renal dysfunction and injury caused by oxidative and nitrosative stress of the kidney. Am J Nephrol24: 165-177.
30.
Chaudiere, J. and Ferrari-Iliou, R. (1999) Intracellular antioxidants from chemical to biochemical mechanisms. Food Chem Toxicol37: 949-962.
31.
Chu, F.F., Doroshow, J.H. and Esworthy, R.S. (1993) Expression,characterization and tissue distribution of a new cellular selenium dependent glutathione peroxidase, GSH-Px-GI. J Biol Chem268: 2571-2576.
32.
Cluzel, M., Damon, M., Chanez, P., Bousquet, J., Crastes de Paulet, A., Michel, F.B. et al. (1987) Enhanced alveolar cell luminol-dependent chemiluminescence in asthma. J Allergy Clin Immunol80: 195-201.
33.
Comhair, S.A., Bhathena, P.R., Farver, C., Thunnissen, F.B., Erzurum, S.C. et al. (2001) Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells. FASEB J15: 70-78.
34.
Comhair, S.A., Bhathena, P.R., Dweik, R.A., Kavuru, M. and Erzurum, S.C. (2000) Rapid loss of superoxide dismutase activity during antigen-induced asthmatic response. Lancet355: 624.
35.
Comhair, S.A., Ricci, K.S., Arroliga, M., Lara, A.R., Dweik, R.A., Song, W. et al. (2005) Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Am J Respir Crit Care Med172: 306-313.
36.
Conner, E.M. and Grisham, M.B. (1996) Inflammation, free radicals, and antioxidants. Nutrition12: 274-277.
37.
Corradi, M., Folesani, G., Andreoli, R., Manini, P., Bodini, A., Piacentini, G. et al. (2003) Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. Am J Respir Crit Care Med167: 395-399.
38.
Davies, K.J. (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp61: 1-31.
39.
De Raeve, H.R., Thunnissen, F.B.M.J., Kaneko, F.T., Guo, F.H., Lewis, M., Kavuru, M.S. et al. (1997) Decreased Cu, Zn-SOD activity in asthmatic airway epithelium: Correction by inhaled corticosteroid in vivo. Am J Physiol272: L148-L154.
40.
Dickinson, D.A. and Forman, H.J. (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol64: 1019-1026.
41.
Doctrow, S.R., Huffman, K., Marcus, C.B., Musleh, W., Bruce, A., Baudry, M. et al. (1997) Salen-manganese complexes: combined superoxide dismutase/catalase mimics with broad pharmacological efficacy. Adv Pharmacol38: 247-269.
42.
Donnelly, L.E., Newton, R., Kennedy, G.E., Fenwick, P.S., Leung, R.H., Ito, K. et al. (2004) Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol287: L774-L783.
43.
Droge, W. (2002) Free radicals in the physiological control of cell function. Physiol Rev82: 47-95.
44.
Dubuisson, M., Vander, S.D., Clippe, A., Etienne, F., Nauser, T., Kissner, R. et al. (2004) Human peroxiredoxin 5 is a peroxynitrite reductase. FEBS Lett571: 161-165.
45.
Ekmekci, O.B., Donma, O., Ekmekci, H., Yildirim, N., Uysal, O., Sardogan, E. et al. (2006) Plasma paraoxonase activities, lipoprotein oxidation, and trace element interaction in asthmatic patients. Biol Trace Elem Res111: 41-52.
46.
Ercan, H., Birben, E., Dizdar, E.A., Keskin, O., Karaaslan, C., Soyer, O.U. et al. (2006) Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma. J Allergy Clin Immunol118: 1097-1104.
47.
Evans, P. and Halliwell, B. (2001) Micronutrients: oxidant/antioxidant status. Br J Nutr85: S67-S74.
48.
Filomeni, G., Rotilio, G. and Ciriolo, M.R. (2002) Cell signalling and the glutathione redox system . Biochem Pharmacol64: 1057-1064.
49.
Flohe, I. (1989) The selenoprotien glutathione peroxidase. In Dolphin, D., Poulson, R. and Naamovic, O. (eds) Glutathione Chemical, Biochemical and Medical Aspects - Part A. New York: John Wiley and Sons Inc., 643-731.
50.
Fogarty, A., Lewis, S., Weiss, S. and Britton, J. (2000) Dietary vitamin E, IgE concentrations and atopy . Lancet356: 1573-1574.
51.
Fogarty, A., Lewis, S.A., Scrivener, S.L., Antoniak, M., Pacey, S., Pringle, M. et al. (2006) Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med100: 174-179.
52.
Fogarty, A., Lewis, S.A., Scrivener, S.L., Antoniak, M., Pacey, S., Pringle, M. et al. (2003) Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial. Clin Exp Allergy33: 1355-1359.
53.
Folkerts, G., Kloek, J., Muijsers, R.B.R. and Nijkamp, F.P. (2001) Reactive nitrogen and oxygen species in airway inflammation. Eur J Pharmacol429: 251-262.
54.
Ghiselli, A., Serafini, M., Natella, F. and Scaccini, C. (2000) Total antioxidant capacity to assess redox status: critical view and experimental data. Free Radic Biol Med29: 1106-1114.
55.
Gilliland, F.D., Berhane, K.T., Li, Y.F., Gauderman, J., McConnell, R. and Peters, J. (2003) Children's lung function and antioxidant vitamin, fruit, juice and vegetable intake. Am J Epidemiol158: 576-584.
56.
Gillissen, A., Jaworska, M., Orth, M., Coffiner, M., Maes, P., App, E.M. et al. (1997) N-acystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir Med91: 159-168.
57.
Gromer, S., Urig, S. and Becker, K. (2004) The thioredoxin system-from science to clinic. Med Res Re24: 40-89.
58.
Grundemann, D., Harlfinger, S., Golz, S., Geerts, A., Lazar, A., Berkels, R. et al. (2005) Discovery of the ergothioneine transporter . Proc Natl Acad Sci USA102: 5256-5261.
59.
Haddad, E., McCluskie, K., Birrell, M.A., Dabrowski, D., Pecoraro, M., Underwood, S. et al. (2002) Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammation. J Immunol169: 974-982.
60.
Halliwell, B. (1996) Antioxidants in human health and disease. Ann Rev Nutr16: 33-50.
61.
Halliwell, B. (2000) The antioxidant paradox. Lancet355: 1179-1180.
62.
Halliwell, B. and Cross, C.E. (1994) Oxygen derived species: their relation to human disease and environmental stress. Environ Health Perspect102: 5-12.
63.
Halliwell, B. and Gutteridge, J.M.C. (1996) The antioxidants of human extracellular fluids. Arch Biochem Biophy280: 1-8.
64.
Hanazawa, T., Kharitonov, S.A. and Barnes, P.J. (2000) Increased nitrotyrosine in exhaled breath condensate of patients with asthma. Am J Respir Crit Care Med162: 1273-1276.
65.
Hand, C.E., Taylor, N.J. and Honek, J.F. (2005) Ab initio studies of the properties of intracellular thiols ergothioneine and ovothiol. Bioorg Med Chem Lett15: 1357-1360.
66.
Harik-Khan, R.I., Muller, D.C. and Wise, R.A. (2004) Serum vitamin levels and the risk of asthma in children. Am J Epidemiol159: 351-357.
67.
Heffner, J.A. and Repine, J.E. (1989) State of the art: pulmonary strategies of antioxidant defense. Am Rev Respir Dis140: 531-554.
68.
Heiss, L.N., LancasterJr., Corbett, J.A. and Goldman, W.E. (1994) Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of pertussis. Proc Natl Acad Sci USA91: 267-270.
69.
Henderson, W.R., Chi, E.Y., Teo, J.L., Nguyen, C. and Kahn, M. (2002) A small molecule inhibitor of redox-regulated NF-kappa B and activator protein-1 transcription blocks allergic airway inflammation in a mouse asthma model. J Immunol169: 5294-5299.
70.
Henricks, P.A. and Nijkamp, F.P. (2001) Reactive oxygen as mediators in asthma. Pulm Pharmacol Ther14: 409-20.
71.
Hijazi, N., Abalkhail, B. and Seaton, A. (2000) Diet and childhood asthma in a society in transition: a study in urban and rural Saudi Arabia. Thorax55: 775-779.
72.
Holmgren, A. (2000) Antioxidant function of thioredoxin and glutaredoxin systems. Antioxid Redox Signal2: 811-820.
73.
Horváth, I., Donnelly, L.E., Kiss, A., Kharitonov, S.A., Tim, S., Chung, K.F. et al. (1998) Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma. Am J Crit Care Med158: 1042-1046.
74.
Hu, G. and Cassano, P. (2000) Antioxidants and pulmonary function: the third National Health and Nutrition Examination Survey (NHANES III). Am J Epidemiol151: 975-981.
75.
Izumi, M., McDonald, M.C., Sharpe, M.A., Chatterjee, P.K. and Thiemermann, C. (2002) Superoxide dismutase mimetics with catalase activity reduce the organ injury in hemorrhagic shock. Shock18: 230-235.
76.
Jacobson, G.A., Yee, K.C. and Ng, C.H. (2007) Elevated plasma glutathione peroxidase concentration in acute severe asthma: comparison with plasma glutathione peroxidase activity, selenium and malondialdehyde. Scand J Clin Lab Invest67: 423-430.
77.
Janssen, Y.M.W., van Houten, B., Borm, P.J.A. and Mossman, B.T.(1993) Cell and tissue responses to oxidative damage. Lab Invest69: 261-274.
78.
Jozsef, L. and Filep, J.G. (2003) Selenium-containing compounds attenuate peroxynitrite-mediated NF-kappaB and AP-1 activation and interleukin-8 gene and protein expression in human leukocytes. Free Radic Biol Med35: 1018-1027.
79.
Kalayci, O., Besler, T., Kilinc, K., Sekerel, B.E. and Saraclar, Y. (2000) Serum levels of antioxidant vitamins (alpha tocopherol, beta carotene and ascorbic acid) in children with bronchial asthma. Turkish J Pediatr42: 17-21.
80.
Kaminsky, D.A., Mitchell, J., Carroll, N., James, A., Soultanakis, R. and Janssen, Y. (1999) Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma. J Allergy Clin Immunol104: 747-754.
81.
Kanazawa, H., Kurihara, N., Hirata, K. and Takeda, T. (1991) The role of free radicals in airway obstruction in asthmatic patients. Chest100: 1319-1322.
82.
Kanazawa, H., Shiraishi, S., Hirata, K. and Yoshikawa, J. (2002) Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma. Thorax57: 509-512.
83.
Katsoulis, K., Kontakiotis, T., Leonardopoulos, I., Kotsovilli, A., Legakis, I.N. and Patakas, D. (2003) Serum total antioxidant status in severe exacerbation of asthma: correlation with severity of disease. J Asthma40: 847-854.
84.
Katsumata, U., Miura, M., Ichinose, M., Kimura, K., Takahashi, T., Inoue, H. and Takishima, T. (1990) Oxygen radicals produce airway constriction and hyperresponsiveness in anesthetized cats. Am Rev Respir Dis141: 1158-1161.
85.
Kelly, C., Ward, C., Stenton, C.S., Bird, G., Hendrick, D.J. and Walters, E.H. (1988) Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness. Thorax43: 684-692.
86.
Kelly, F.J., Mudway, I., Blomberg, A., Frew, A. and Sandström, T. (1999) Altered lung antioxidant status in patients with mild asthma. Lancet354: 482-483.
87.
Kinnula, V.L. (2005) Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases. Thorax60: 693-700.
88.
Kinnula, V.L. and Crapo, J.D. (2003) Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med167: 1600-1619.
89.
Kinnula, V.L., Lehtonen, S., Kaarteenaho-Wiik, R., Lakari, E., Pääkkö, P., Kang, S.W. et al. (2002) Cell specific expression of peroxiredoxins in human lung and pulmonary sarcoidosis. Thorax57: 157-164.
90.
Kirkman, H.N., Rolfo, M., Ferraris, A.M. and Gaetani, G.F. (1999) Mechanisms of protection of catalase by NADPH. Kinetics and stoichiometry. J Biol Chem274: 13908-13914.
91.
Knekt, P., Kumpulainen, J., Jarvinen, R., Rissanen, H., Heliovaara, M., Reunanen, A. et al. (2002) Flavonoid intake and risk of chronic diseases . Am J Clin Nutr76: 560-568.
92.
Koike, Y., Hisada, T., Utsugi, M., Ishizuka, T., Shimizu, Y., Ono, A. et al. (2007) Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice. Am J Respir Cell Mol Biol37: 322-329.
93.
Kurosawa, M., Kobayashi, H. and Nakano, M. (1993) Cu- Zn superoxide dismutase activities in platelets from stable bronchial asthmatic patients. Int Arch Allergy Immunol101: 61-65.
94.
Lee, K.S., Kim, S.R., Park, H.S., Park, S.J., Min, K.H., Lee, K.Y. et al. (2007a) A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha. Exp Mol Med39: 756-768.
95.
Lee, S.H., Park, H.H., Kim, J.E., Kim, J.A., Kim, Y.H., Jun, C.D. et al. (2007b) Allose gallates suppress expression of pro-inflammatory cytokines through attenuation of NF-kappaB in human mast cells. Planta Med73: 769-773.
96.
Lynch, R.E. and Fridovich, I. (1978) Permeation of the erythrocyte stroma by superoxide radical. J Biol Chem253: 4697-4699.
97.
MacNee, W. and Rahman, I. (1999) Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. Am J Respir Crit Care Med160: 58-65.
98.
MacNee, W., Bridgeman, M.M., Marsden, M., Drost, E., Lannan, S., Selby, C. and Donaldson, K. (1991) The effects of N-acetylcysteine and glutathione on smoke-induced changes in lung phagocytes and epithelial cells. Am J Med91: 60-66.
99.
MacPherson, J.C., Comhair, S.A., Erzurum, S.C., Klein, D.F., Lipscomb, M.F., Kavuru, M.S. et al. (2001) Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma characterization of pathways available to eosinophils for generating reactive nitrogen species. J Immunol166: 5763-5772.
100.
Malmberg, K.J., Arulampalam, V., Ichihara, F., Petersson, M., Seki, K., Andersson, T. et al. (2001) Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation . J Immunol167: 2595-2601.
101.
Manna, S.K., Mukhopadhyay, A. and Aggarwal, B.B. (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol164: 6509-6519.
102.
Mao, G.D. and Poznansky, M.J. (1992) Electron spin resonance study on the permeability of superoxide radicals in lipid bilayers and biological membranes. FEBS Lett305: 233-236.
103.
McCord, J.M. and Fridovich, I. (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem244: 6049-6055.
104.
McKeever, T.M. and Britton, J. (2004) Diet and asthma. Am J Respir Crit Care Med170: 725-729.
105.
Misso, N.L., Brooks-Wildhaber, J., Ray, S., Vally, H. and Thompson, P.J. (2005) Plasma concentrations of dietary and nondietary antioxidants are low in severe asthma. Eur Respir J26: 257-264.
106.
Misso, N.L.A., Powers, K.A., Gillon, R.C., Stewart, G.A. and Jhompson, P.J. (1996) Reduced platelet glutathione reductase activity and serum selenium concentration in atopic asthmatics patients. Clin ExpAllergy26: 48-54.
107.
Mohan, I.K. and Das, U.N. (1997) Oxidant stress, antioxidants, nitric oxide and essential fatty acids in bronchial asthma. Med Sci Res25: 307-309.
108.
Moncada, S. and Higgs, A. (1993) The L-arginine-nitric oxide pathway. N Engl J Med329: 2002-2012.
109.
Montuschi, P., Corradi, M., Ciabattoni, G., Nightingale, J., Kharitonov, S.A. and Barnes, P.J. (1999) Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients. Am J Respir Crit Care Med160: 216-220.
110.
Nadeem, A., Chhabra, S.K., Masood, A. and Raj, H.G. (2003) Increased oxidative stress and altered levels of antioxidants in asthma. J Allergy Clin Immunol111: 72-78.
111.
Nadeem, A., Raj, H.G. and Chhabra, S.K. (2005) Increased oxidative stress in acute exacerbations of asthma. J Asthma42: 45-50.
112.
Neuman, I., Nahum, H. and Ben-Amotz, A. (1999) Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene. Ann Allergy Asthma Immunol82: 549-553.
113.
Neuman, I., Nahum, H. and Ben-Amotz, A. (2000) Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy55: 1184-1189.
114.
Nguyen, C., Teo, J.L., Matsuda, A., Eguchi, M., Chi, E.Y., Henderson Jr, W.R. et al. (2003) Chemogenomic identification of ref-1/AP-1 as a therapeutic target for asthma. Proc Natl Acad Sci USA100: 1169-1173.
115.
Novak, Z., Nemeth, I., Gyurkovits, K., Varga, S.I. and Matkovics, B. (1991) Examination of the role of oxygen free radicals in bronchial asthma in childhood. Clinica Chimica Acta201: 247-252.
116.
Ochs-Balcom, H.M., Grant, B.J., Muti, P., Sempos, C.T., Freudenheim, J.L., Browne, R.W. et al. (2006) Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD. Eur J Clin Nutr60: 991-999.
117.
Okamura, M. (1979) Uptake of L-ascorbic acid and L-dehydroascorbic acid by human erythrocytes and HeLa cells. J Nutr Sci Vitaminol (Tokyo) 25: 269-279.
118.
Olopade, C.O., Zakkar, M., Swedler, W.I. and Rubinstein, I. (1997) Exhaled pentane levels in acute asthma. Chest111: 862-865.
119.
Paredi, P., Kharitonov, S.A. and Barnes, P.J. (2000) Elevation of exhaled ethane concentration in asthma . Am J Respir Crit Care Med162: 1450-1454.
120.
Pearson, P.J., Lewis, S.A., Britton, J. and Fogarty, A. (2004) Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial. Thorax59: 652-656.
121.
Picado, C., Deulofeu, R., Lleonart, R., Agustí, M., Mullol, J., Quintó, L. and Torra, M. (2001) Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity. Allergy56: 43-49.
122.
Powell, C.V.E., Nash, AA, Powers, H.J. and Primhak, R.A. (1994) Antioxidant status in asthma. Pediatr Pulmonol18: 34-38.
123.
Qin, J., Clore, G.M., Kennedy, W.M., Huth, J.R. and Gronenborn, A.M. (1995) Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF Kappa B. Structure3: 289-297.
124.
Rahman, I. and MacNee, W. (2002) Reactive oxygen species. In Barnes, P.J.,Drazen, J.,Rennard, S. et al. (eds) Asthma and COPD. London: Academic Press, 243-254.
125.
Rahman, I. and MacNee, W. (1999) Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease. Am J Physiol277: L1067-L1088.
126.
Rahman, I., Morrison, D., Donaldson, K. and Mac Nee, W. (1996) Systemic oxidative stress in asthma, COPD and smokers . Am J Respir Crit Care Med159: 1055-1060.
127.
Ricciardolo, F.L.M., Sterk, P.J., Gaston, B. and Folkerts, G. (2004) Nitric oxide in health and disease of the respiratory system. Physiol Rev84: 731-765.
128.
Riccioni, G., Bucciarelli, T., Mancini, B., Di Ilio, C., Della Vecchia, R. and D'Orazio, N. (2007) Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study. J Asthma44: 429-432.
129.
Romieu, I., Barraza-Villarreal, A., Escamilla-Nuñez, C., Almstrand, A.C., Diaz-Sanchez, D., Sly, P.D. et al. (2008) Exhaled breath malondialdehyde as a marker of effect of exposure to air pollution in children with asthma. J Allergy Clin Immunol121: 903-909.
130.
Romieu, I., Sienra-Monge, J.J., Ramírez-Aguilar, M., Téllez-Rojo, M.M., Moreno-Macías, H., Reyes-Ruiz, N.I. et al. (2002) Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med166: 703-709.
131.
Rubin, R.N., Navon, L. and Cassano, P.A. (2004) Relationship of serum antioxidants to asthma prevalence in youth. Am J Respir Crit Care Med169: 393-398.
132.
Sackesen, C., Ercan, H., Dizdar, E., Soyer, O., Gumus, P., Tosun, B.N. et al. (2008) A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma. J Allergy Clin Immunol [Epub ahead of print].
133.
Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y. et al. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J17: 2596-2606.
134.
Saleh, D., Ernst, P., Lim, S., Barnes, P.J. and Giaid, A. (1998) Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of NO synthase: effect of inhaled glucocorticoid. FASEB J12: 929-37.
135.
Salvemini, D., Wang, Z.Q., Zweier, J.L., Samouilov, A., Macarthur, H., Misko, T.P. et al. (1999) A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science286: 304-306.
136.
Sareila, O., Hämäläinen, M., Nissinen, E., Kankaanranta, H. and Moilanen, E. (2008) Orazipone inhibits activation of inflammatory transcription factors nuclear factor-kappa B and signal transducer and activator of transcription 1 and decreases inducible nitric-oxide synthase expression and nitric oxide production in response to inflammatory stimuli. J Pharmacol Exp Ther324: 858-866.
137.
Schafer, F.Q. and Buettner, G.R. (2001) Redox environment of the cells as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med30: 1191-1212.
138.
Schünemann, H.J., Grant, B.J.B., Freudenheim, J.L., Muti, P., Browne, R.W., Drake, J.A. et al. (2001) The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population. Am J Respir Crit Care Med163: 1246-1255.
139.
Schünemann, H.J., Muti, P., Freudenheim, J.L., Armstrong, D., Browne, R. and Klocke, R.A. (1997) Oxidative stress and lung function. Am J Epidemiol146: 939-948.
140.
Schwartz, J. and Weiss, S.T. (1994) Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am J Clin Nutr59: 110-114.
141.
Seaton, A., Godden, D.J. and Brown, K. (1994) Increase in asthma: a more toxic environment or a more susceptible population? Thorax49: 171-174.
142.
Shanmugasundaram, K.R., Kumar, S.S. and Rajajee, S. (2001) Excessive free radical generation in the blood of children suffering from asthma. Clin Chim Acta305: 107-114.
143.
Sienra-Monge, J.J., Ramírez-Aguilar, M., Moreno-Macías, H., Reyes-Ruiz, N.I., Del Rio-Navarro, B.E., Ruiz-Navarro, M.X. et al. (2004) Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone. Clin Exp Immunol138: 317-322.
144.
Sies, H. (1999) Glutathione and its role in cellular functions . Free Radic Biol Med27: 916-921.
145.
Smith, L.J., Houston, M. and Anderson, J. (1993) Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma. Am Rev Respir Dis147: 1461-1464.
146.
Smith, L.J., Shamsuddin, M., Sporn, P.H.S., Denenberg, M. and Andrrson, J. (1997) Reduced superoxide dismutase in lung cells of patients with asthma. Free Rad Biol Med22: 1301-1307.
147.
Soutar, A., Seaton, A. and Brown, K. (1997) Bronchial reactivity and dietary antioxidants. Thorax52: 166-170.
148.
Stahl, W., Ale-Agha, N. and Polidori, M.C. (2002) Non-antioxidant properties of carotenoids. Biol Chem383: 553-558.
149.
Takahashi, K., Avissar, N., Whitin, J. and Cohen, H. (1987) Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme. Arch Biochem Biophys256: 677-686.
150.
Tecklenburg, S.L., Mickleborough, T.D., Fly, A.D., Bai, Y. and Stager, J.M. (2007) Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med101: 1770-1778.
151.
Tekin, D., Ayse Sin, B., Mungan, D., Misirligil, Z. and Yavuzer, S. (2000) The antioxidant defense in asthma. J Asthma37: 59-63.
152.
Toth, K.M., Clifford, D.P., Berger, E.M., White, C.W. and Repine, J.E. (1984) Intact human erythrocyte prevent hydrogen peroxide mediated damage to isolated perfused rat lungs and cultured bovine pulmonary artery endothelial cells. J Clin Invest74: 292-295.
153.
Trenga, C.A., Koenig, J.Q. and Williams, P.V. (2001) Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma. Arch Environ Health56: 242-249.
154.
Troisi, R.J., Willett, W.C., Weiss, S.T., Trichopoulos, D., Rosner, B. and Speizer, F.E. (1995) A prospective study of diet and adult-onset asthma . Am J Respir Crit Care Med151: 1401-1408.
155.
Tuder, R.M., Zhen, L., Cho, C.Y., Taraseviciene-Stewart, L., Kasahara, Y., Salvemini, D. et al. (2003) Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade . Am J Respir Cell Mol Biol29: 88-97.
156.
Van Asbeck, B.S., Hoidal, J., Vercelloti, G.M. et al. (1985) Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione. Science227: 756-59.
157.
Vignola, A.M., Chiappara, G., Gagliardo, R., Gjomarkaj, M., Merendino, A., Siena, L. et al. (2000) Apoptosis and airway inflammation in asthma . Apoptosis5: 473-485.
158.
Vural, H. and Uzun, K. (2000) Serum and red blood cell antioxidant status in patients with bronchial asthma. Can Respir J7: 476-480.
159.
Wagner, E.S., White, W., Jennings, M. and Bennett, K. (1987) The extrapment of 14C ascoprbic acid in human erythrocytes . Biochem Biophys Acta902: 133-136.
160.
Wali, R.K., Jaffe, S., Kumar, D., Sorgente, N. and Kalra, V.K. (1987) Increased adherence of oxidant-treated human and bovine erythrocytes to cultured endothelial cells. J Cell Physiol133: 25-36.
161.
Winterbourn, C.C. and Stern, A. (1987) Human red cells scavenge extrcellular hydrogen peroxide and inhibit formation of hypochlorous acid and hyroxyl radical. J Clin Invest80: 1486-1491.
162.
Wood, L.G., Fitzgerald, D.A., Gibson, P.G., Cooper, D.M. and Garg, M.L. (2000) Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma. Lipids35: 967-974.
163.
Wood, L.G., Garg, M.L., Blake, R.J., Garcia-Caraballo, S. and Gibson, P.G. (2005) Airway and circulating levels of carotenoids in asthma and healthy controls. J Am Coll Nutr24: 448-455.
164.
Wood, L.G., Garg, M.L., Blake, R.J., Simpson, J.L. and Gibson, P.G. (2008a) Oxidized vitamin E and glutathione as markers of clinical status in asthma. Clin Nutr [Epub ahead of print].
165.
Wood, L.G., Garg, M.L., Powell, H. and Gibson, P.G. (2008b) Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept. Free Radic Res42: 94-102.
166.
Wu, P., Roberts, L.J. II, Shintani, A.K., Sheller, J.R., Minton, P.A., Higgins, S.B. et al. (2007) Changes in urinary dinor dihydro F(2)-isoprostane metabolite concentrations, a marker of oxidative stress, during and following asthma exacerbations. Free Radic Res41: 956-962.
167.
Wu, W., Chen, Y. and Hazen, S.L. (1999) Eosinophil peroxidase nitrates protein tyrosyl residues. Implications for oxidative damage by nitrating intermediates in eosinophilic inflammatory disorders. J Biol Chem274: 25933-25944.
168.
Wu, W., Samoszuk, M.K., Comhair, S.A., Thomassen, M.J., Farver, C.F., Dweik, R.A. et al. (2000) Eosinophils generate brominating oxidants in allergen-induced asthma. J Clin Invest105: 1455-1463.
169.
Yamada, Y., Nakamura, H., Adachi, T., Sannohe, S., Oyamada, H., Kayaba, H. et al. (2003) Elevated serum levels of thioredioxin in patients with acute exacerbation of asthma. Immunol Lett86: 199-205.
170.
Zelko, I.N., Mariani, T.J. and Folz, R.J. (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med33: 337-349.
171.
Zhang, M., Nomura, A., Uchida, Y., Iijima, H., Sakamoto, T., Iishii, Y. et al. (2002) Ebselen suppresses late airway responses and airway inflammation in guinea pigs, Free Radic Biol Med32: 454-464.
