Abstract
Oxidative stress is believed to play an important role in the pathophysiology of asthma. Recently discovered F2-isoprostanes, of which 8-iso-PGF2α is the most well-known isomer, have emerged as the most reliable marker of in vivo oxidative stress. The aim of this study was to examine 8-iso-PGF2α as a biomarker of oxidative stress in mild asthma in relation to endogenous and dietary antioxidant protection. Total (free and esterified) plasma 8-iso-PGF2α, plasma dietary antioxidants (vitamins E and C,β-carotene, Zn, and Se), and erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase) were measured in 15 mild asthmatics and 15 age-and sex-matched controls. Total plasma 8-iso-PGF2α levels [median (quartile 1-quartile 3)] were significantly increased in the sthmatics [213 pg/mL (122–455) vs. 139 pg/mL (109–174), P=0.042]. The 8-iso-PGF2α levels were found to be associated with clinical asthma severity (P=0.044) and inhaled corticosteroid use (P=0.027) in asthmatics. No differences were observed in the plasma dietary antioxidant vitamins. The asthmatics had significantly lower plasma levels of Zn (P=0.027) and Se (P=0.006). Plasma Se correlated negatively with 8-iso-PGF2α (r=−0.725, P=0.002). No differences between the groups were observed for glutathione peroxidase or superoxide dismutase, however, superoxide dismutase activity was negatively associated with asthma severity (P=0.042). In conclusion, oxidative stress is increased in mild asthmatics, as reflected by increased plasma levels of 8-iso-PGF2α and a deficiency in plasma Zn and Se. The isoprostane 8-iso-PGF2α may provide a useful tool in intervention studies aimed at improving clinical status in asthma.
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Abbreviations
- BHT:
-
butylated hydroxytoluene
- EIA:
-
enzyme immunoassay
- FEV1:
-
forced expiratory volume in one second
- FVC:
-
forced vital capacity
- GC-MS:
-
gas chromatography-mass spectrometry
- GSHPx:
-
glutathione peroxidase
- Hb:
-
hemoglobin
- HPLC:
-
high-performance liquid chromatography
- TCP-MS:
-
inductively coupled plasma-mass spectrometry
- 8-iso-PGF2α :
-
isomer of F2-isoprostane
- MDA:
-
malondialdehyde
- ROS:
-
reactive oxygen species
- SEM:
-
standard error of the mean
- SOD:
-
superoxide dismutase
- TBARS:
-
thiobarbituric acid-reactive substance
- TEAC:
-
Trolox equivalent antioxidant capacity
- TxB2 :
-
tritium-labeled thromboxane
References
Barnes, P.J. (1990) Reactive Oxygen Species and Airway Inflammation, Free Radical Biol. Med. 9, 235–243.
Rahman, I., Morrison, D., Donaldson, K., and MacNee, W. (1996) Systemic Oxidative Stress in Asthma, COPD and Smokers, Am. J. Respir. Crit. Care Med. 154, 1055–1060.
Horvarth, I., Donnelly, L.E., Kiss, A., Kharitonov, S.A., Lim, S., Chung, K.F., and Barnes, P.J. (1998) Combined Use of Exhaled Hydrogen Peroxide and Nitric Oxide in Monitoring Asthma, Am. J. Respir. Crit. Care Med 158, 1042–1046.
Mohan, I.K., and Das, U.N. (1997) Oxidant Stress, Antioxidants, Nitric Oxide and Essential Fatty Acids in Bronchial Asthma, Med. Sci. Res. 25, 307–309.
Flatt, A., Pearce, N., Thomson, C.D., Sears, M., Robinson, M.F., and Beasley, R. (1990) Reduced Selenium in Asthmatic Subjects in New Zealand, Thorax 45, 95–99.
Kadrabova, J., Madaric, A., Koyakicova, Z., Podivinsky, F., Ginter, E., and Gazdik, F. (1996) Selenium Status Is Decreased in Patiens with Intrinsic Asthma, Biol. Trace Elem. Res. 52, 241–248.
Smith, L.J., Shamsuddin, M., Sporn, P.H.S., Denenberg, M., and Anderson, J. (1997) Reduced Superoxide Dismutase in Lung Cells of Patients with Asthma, Free Radical Biol. Med. 22, 1301–1307.
Kurosawa, M., Kobayashi, H., and Nakano, M. (1993) Cu−Zn Superoxide Dismutase Activities in Platelets from Stable Bronchial Asthmatic Patients, Int. Arch. Allergy Immunol. 101, 61–65.
Stone, J., Hinks, L.J., Beasley, R., Holgate, S.T., and Clayton, B.A. (1989) Reduced Selenium Status of Patients with Asthma, Clin. Sci. 77, 495–500.
Kelly, F.J., Mudway, I., Blomberg, A., Frew, A., and Sandstrom, T. (1999) Altered Lung Antioxidant Status in Patients with Mild Asthma, Lancet 354, 482–483.
Cluzel, M., Damon, M., Chanez, P., Bousquet, J., Crastes de Paulet, A., Michel, F.B., and Bodard, P. (1987) Enhanced Alveolar Cell Luminol-dependent Chemiluminescence in Asthma, J. Allergy Clin. Immunol. 80, 195–201.
Chilvers, E.R., Garratt, H., Whyte, M.K.B., Fink, R., and Ind, P.W. (1989) Absence of Circulating Products of Oxygen-Derived Free Radicals in Acute Severe Asthma, Eur. Respir. J. 2, 950–954.
Pincemail, J., Defraigne, J.O., and Limet, R. (1996) Oxidative Stress in Clinical Situations—Fact or Fiction? Eur. J. Anaesthesiol. 13, 219–234.
Halliwell, B., and Grootveld, M. (1987) The Measurement of Free Radical Reactions in Humans, FEBS Lett. 213, 9–14.
Montuschi, P., Ciabattoni, G., Paredi, P., Pantelidis, P., du Bois, R.M., Kharitonov, S.A., and Barnes, P.J. (1998) 8-Isoprostane as a Biomarker of Oxidative Stress in Interstitial Lung Diseases, Am. J. Respir. Crit. Care Med. 158, 1524–1527.
Morrow, J.D., and Roberts, L.J. (1997) The Isoprostanes—Unique Bioactive Products of Lipid Peroxidation, Prog. Lipid Res 36, 1–21.
Awad, J.A., Roberts, L.J., Burk, R.F., and Morrow, J.D. (1996) Isoprostanes—Prostaglandin-like Compounds Formed in vivo Independently of Cyclooxygenase, Gastroenterol. Clin. North America 25, 409–427.
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 Condensation in Asthma Patients, Am. J. Respir. Crit. Care Med. 160, 216–220.
Anonymous (1998) Asthma Management Handbook, 4th edn., National Asthma Campaign, Melbourne, Australia.
Norzila, M.Z., Fakes, K., Henry, R.L., Simpson, J., and Gibson, P.G. (2000) Interleukin 8 Secretion and Neutrophil Recruitment Accompanies Induced Sputum Eosinophil Activation in Children with Acute Asthma, Am. J. Respir. Crit. Care Med. 161, 769–774.
Knudson, R.J., Slatin, R.C., Lebowitz, M.D., and Burrows, B. (1976) The Maximal Expiratory Flow-Volume Curve: Normal Standards, Variability and Effects of Age, Am. Rev. Respir. Dis. 113, 587–600.
Collins, C.E., Quaggiottio, P., Wood, L., O'Loughlin, E.V., Henry, R.L., and Garg, M.L. (1999) Elevated Plasma Levels of F2α Isoprostane in Cystic Fibrosis, Lipids. 34, 551–556.
Block, G. (1982) A Review of Validations of Dietary Assessment Methods, A. J. Epidemiol. 115, 492–505.
Goodhill, C., Diet/1 Nutrient Calculation Software, 20 Westborne St., Highgate Hill, Brisbane, Queensland, Australia 4101.:(c) Xyris Software, 1992.
Bland, M. (1987) An Introduction to Medical Statistics, 1st edn., pp. 216–240, Oxford University Press, Oxford.
DeRaeve, H.R., Thunnissen, F.B.M.J., Kaneko, F.T., Guo, F.H., Lewis, M., Kavuru, M.S., Secic, M., Thomassen, M.J., and Erzurum, S.C. (1997) Decreased Cu,Zn-SOD Activity in Asthmatic Airway Epithelium: Correction by Inhaled Corticosteroid in vivo, Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16), L148-L154.
Kang, H.K., Morrow, J.D., Roberts, L.J., Newman, J.H., and Banerjee, M. (1993) Airway and Vascular Effects of 8-Epi-prostaglandin F2α in Isolated Perfused Rat Lung, J. Appl. Physiol. 74, 460–465.
Klein, T., Reutter, F., Schweer, H., and Nusing, R.M. (1997) Generation of the Isoprostane 8-Epi-prostaglandin F2 alpha in vitro and in vivo via the Cyclooxygenases, J. Pharmacol. Exp. Ther. 282, 1658–1665.
Pratico, D., Basili, S., Vieri, M., Cordova, C., Violi, F., and Fitzgerald, G.A. (1998) Chronic Obstructive Pulmonary Disease Is Associated with an Increase in Urinary Levels of Isoprostane F2α III, an Index of Oxidant Stress, Am. J. Respira. Crit. Care Med. 158, 1709–1714.
Delanty, N., Reilly, M., Pratico, D., Fitzgerald, D.J., Lawson, J.A., and Fitzgerald, G.A. (1996) 8-Epi-PGF2α Specific Analysis of an Isoeicosanoid as an Index of Oxidant Stress in vivo, Br. J. Clin. Pharmacol. 42, 15–19.
Morrow, J.D., Frei, B., Longmire, A.W., Gaziano, J.M., Lynch, S.M., Shyr, Y., Strauss, W.E., Oates, J.A., and Roberts, L.J. (1995) Increase in Circulating Products of Lipid Peroxidation (F2-isoprostanes) in Smokers, N. Engl. J. Med. 332, 198–203.
Malvy, J.M.D., Lebranchu, Y., Richard, M.J., Arnaud, J., and Favier, A. (1993) Oxidative Metabolism and Severe Asthma in Children, Clin. Chem. Acta 218, 117–120.
Bray, T.M., and Bettger, W.J. (1990) The Physiological Role of Zinc as an Antioxidant, Free Radical Biol. Med. 8, 281–291.
Taylor, C.G., Bettger, W.J., and Bray, T.M. (1988) The Effect of Dietary Zinc or Copper Deficiency on the Primary Free Radical Defense System in Rats, J. Nutr. 118, 613–621.
Behne, D., and Wolters, W. (1979) Selenium Content and Glutathione Peroxidase Activity in the Plasma and Erythrocytes of Non-pregnant and Pregnant Women, J. Clin. Chem. Clin. Biochem. 17, 133–135.
Burk, R.F., Hill, K.E., Awad, J.A., Morrow, J.D., and Lyons, P.R. (1995) Liver and Kidney Necrosis in Selenium-Deficient Rats Depleted of Glutathione, Lab. Invest. 72, 723–730.
Powell, C.V.E., Nash, A.A., Powers, H.J., and Primhak, R.A. (1994) Antioxidant Status in Asthma, Pediatr. Pulmonol. 18, 34–38.
Aderele, W.I., Ette, S.I., Oduwole, O., and Ikpeme, S.J. (1985) Plasa Vitamin C (ascorbic acid) Levels in Asthmatic Children, Afr. J. Med. Sci. 14, 115–120.
Hasselmark, L., Malmgren, R., Zetterstrom, O., and Unge, G. (1993) Selenium Supplementation in Intrinsic Asthma, Allergy 48, 30–36.
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Wood, L.G., Fitzgerald, D.A., Gibson, P.C. et al. Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma. Lipids 35, 967–974 (2000). https://doi.org/10.1007/s11745-000-0607-x
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DOI: https://doi.org/10.1007/s11745-000-0607-x