Oxidative stress in allergic respiratory diseases

doi:10.1067/mai.2002.126780

Journal of Allergy and Clinical Immunology

Volume 110, Issue 3, September 2002, Pages 349-356

https://doi.org/10.1067/mai.2002.126780 Get rights and content

Abstract

There is ample evidence that allergic disorders, such as asthma, rhinitis, and atopic dermatitis, are mediated by oxidative stress. Excessive exposure to reactive oxygen and nitrogen species is the hallmark of oxidative stress and leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as a result of inflammation but also from environmental exposure to air pollution and cigarette smoke. The specific localization of antioxidant enzymes in the lung and the rapid reaction of nitric oxide with reactive oxygen species, such as superoxide, suggest that antioxidant enzymes might also function as cell-signaling agents or regulators of cell signaling. Therapeutic interventions that decrease exposure to environmental reactive oxygen species or augment endogenous antioxidant defenses might be beneficial as adjunctive therapies for allergic respiratory disorders. (J Allergy Clin Immunol 2002;110:349-56.)

Section snippets

Reactive oxygen species defined

The major function of the respiratory and cardiovascular system is the delivery of oxygen for use in aerobic energy production by means of oxidative phosphorylation. The features that make oxygen ideal for aerobic energy production (ie, atmospheric abundance and a high affinity for electrons) are also its Achilles' heel. For instance, one electron addition to oxygen produces superoxide, a second electron yields hydrogen peroxide, and a third electron leads to the formation of the hydroxyl

Sources of reactive oxygen species

Normal metabolic processes in all cells are the major source of reactive oxygen species (Fig 3).

. Reactive oxygen species and antioxidant enzymes in airways. A, Environmental sources include ozone (O ₃) and hydrogen peroxide (H ₂O ₂) from air pollution and cigarette smoke. Intracellular sources include mitochondrial respiration, xanthine oxidase (XO) , and P450 and cytochrome b5 enzymes; hydrogen peroxide is a product of superoxide dismutases (SOD) , such as Cu,Zn SOD and mitochondrial DOS

Measurement and toxicity of reactive oxygen species

Electron spin resonance is the only method that directly measures free radicals, but the evanescent nature of many reactive oxygen species has made them difficult to measure in vivo, and instead many investigators use spin trapping to trap the free radical in a more stable molecule that can be readily measured in biologic systems. Recently, the ability to collect and analyze exhaled condensates has allowed for the direct assessment of hydrogen peroxide and nitric oxide in allergic respiratory

Antioxidant defenses

The primary defense against reactive oxygen species is endogenous antioxidants, which can be subdivided into enzymatic and nonenzymatic categories. The enzymatic antioxidants include the families of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione S-transferase, and thioredoxin. Furthermore, each family has isozymes that are distinguished primarily by their distribution. For instance, the 3 mammalian SODs are cytosolic (SOD1), mitochondrial (SOD2), and extracellular

Asthma

Many observations suggest that oxidative stress plays an important role in the pathogenesis of asthma. Although it is difficult to get direct measurements of reactive oxygen species in asthmatic patients, recent studies of exhaled gases from asthmatic patients have shown increased hydrogen peroxide13, 53, 54 and nitric oxide⁵⁵ levels. Furthermore, an increase in reactive oxygen species production is inversely correlated with FEV₁.¹⁴ Airway inflammatory cells are the likely source of these

Therapeutic implications

There are 2 strategies for treating oxidative stress asthma: reducing exposure to reactive oxygen species and augmenting antioxidant defenses. There are already several studies suggesting that reducing exposure to environmental oxidants, such as nitrites and ozone, might decrease asthmatic exacerbations through the attenuation of the activity of pulmonary inflammatory cells.81, 82 For instance, ozone decreases FEV₁ by 12.5% compared with filtered air,⁸² and children playing sports (hence more

Acknowledgements

We thank Drs E. Rand Sutherland, Brian J. Day, and Elizabeth Regan for their critical reading of the manuscript.

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^☆: Supported by National Institutes of Health grants HL-04407 (R.P.B.), HL-31992 (J.D.C), and HL-42444 (J.D.C) and by Incara Pharmaceuticals Inc. Dr Crapo is a consultant for and holds equity in Incara Pharmaceuticals.

^☆☆: Reprint requests: Russell P. Bowler, MD, PhD, National Jewish Medical and Research Center, K736a, 1400 Jackson St, Denver, CO 80206.

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Reviews and Feature ArticlesOxidative stress in allergic respiratory diseases☆,☆☆

Abstract

Section snippets

Reactive oxygen species defined

Sources of reactive oxygen species

Measurement and toxicity of reactive oxygen species

Antioxidant defenses

Asthma

Therapeutic implications

Acknowledgements

Free Radic Biol Med

Arch Biochem Biophys

Mol Med Today

Chest

J Allergy Clin Immunol

Auris Nasus Larynx

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

Free Radic Biol Med

Respir Med

Chest

Free Radic Biol Med

Clin Chim Acta

Respir Physiol

J Biol Chem

Toxicol Lett

Ann Allergy Asthma Immunol

Toxicology

Lancet

Free radicals in biology and medicine

Oxygen and xenobiotic reductase activities of cytochrome P450

Crit Rev Toxicol

Expression of NADH/NADPH oxidase p22phox in human coronary arteries

Circulation

Glucocorticoids inhibit superoxide anion production and p22 phox mRNA expression in human aortic smooth muscle cells

Hypertension

Reactive oxygen species in cell signaling

Am J Physiol Lung Cell Mol Physiol

Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity, and mortality

Am J Respir Crit Care Med

Peroxynitrous acid homolyzes into *OH and *NO2 radicals

Chem Res Toxicol

Nitric oxide generation in aqueous solutions of cigarette smoke and approaches to its origin

Biol Chem

Nitric oxide in cigarette smoke as a mediator of oxidative damage

Int J Exp Pathol

Enhanced production of oxygen radicals in asthma

J Lab Clin Med

Enhanced superoxide production by alveolar macrophages and air-space cells, airway inflammation, and alveolar macrophage density changes after segmental antigen bronchoprovocation in allergic subjects

Am Rev Respir Dis

Spontaneous oxygen radical production at sites of antigen challenge in allergic subjects

Am J Respir Crit Care Med

Increased oxygen species generation in blood monocytes of asthmatic patients

Am Rev Respir Dis

Superoxide and superoxide dismutase in bronchial asthma

Acta Paediatr Jpn

Superoxide generation by hypodense eosinophils from patients with asthma

Am Rev Respir Dis

Increased spontaneous production and generation of superoxide anion by blood neutrophils in patients with asthma

J Asthma

Oxygen radical production by blood eosinophils is reduced during birch pollen season in allergic patients

Clin Exp Allergy

Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma

Am J Respir Crit Care Med

Nitric oxide and asthma: a review

Curr Opin Pulm Med

Nasal nitric oxide is increased in allergic rhinitis

Clin Exp Allergy

Nitric oxide in allergic rhinitis and asthma

Allergy Asthma Proc

Reviews and Feature Articles
Oxidative stress in allergic respiratory diseases☆,☆☆

Peroxynitrous acid homolyzes into OH and NO2 radicals