GSH in Asthma, Bronchitis, and other Pulmonary and Respiratory Diseases (COPD)

Lung diseases: Chronic Obstructive Pulmonary Disease (COPD, including asthma, chronic bronchitis and emphysema) and cystic fibrosis.

  

By Patricia A.L. Kongshavn, Ph.D.

An oxidant/antioxidant imbalance in the lower respiratory tract has been proposed as the mechanism of lung injury in inflammatory lung disorders (1-3). An increased oxygen burden arises from the accumulation of inflammatory cells such as activated alveolar macrophages and neutrophils, which show an exaggerated release of reactive oxygen species (ROS). These ROS not only cause direct damage to the alveolar epithelial cells and parenchyma, but also act as signals perpetuating the inflammatory cascade.

The dominant antioxidant molecule in the lungs, both intracellularly and in the epithelial lung fluid (ELF), is glutathione (GSH) (4). It is thought that extracellular GSH protects the cells from oxidants released by inflammatory cells whilst intracellular GSH neutralizes the ROS produced as a result of normal cell metabolism, as well as detoxifying xenobiotics (4). The concentration of GSH in the ELF of the lower respiratory tract is normally more than 50-fold greater than that found in the plasma (5). In subjects with idiopathic pulmonary fibrosis, GSH deficiency in the ELF has been observed (6).

In order to improve or restore the putative oxidant/antioxidant imbalance in the lower respiratory tract in patients with obstructive pulmonary disease, it is obviously desirable to find an effective therapeutic procedure that would raise the antioxidant component (2,4). Since GSH is the major antioxidant in the lungs, GSH or the pro-drug N-acetyl cysteine (NAC) are logical choices that have been used. This has met with limited success according to Gillisen and Nowak (8). Aerosolized GSH has a low half-life and NAC has a bioavailability of about 10% (8). Moreover NAC can have unpleasant side effects including blurred vision, dysphoria, and gastrointestinal discomfort (9).

Immunocalâ is a whey protein isolate particularly rich in the amino acid cysteine in bioavailable form. It is clinically proven to raise GSH values (9). In a double blind study using healthy young adults, lymphocyte GSH values rose by 35% in subjects fed Immunocal (20g/day for 3 months) whereas there was no change in casein-fed control subjects. Moreover, Dr Lands’ group has published a case report in which a patient with obstructive lung disease was supplemented with Immunocal (20g/day) (7). After one month, whole blood GSH levels and pulmonary function increased dramatically.

References

1. Kelly FJ. Glutathione in defence of the lung. Food Chem Toxicol 1999; 37:963-6.

2. MacNee W. Oxidants/Antioxidants and COPD. Chest 2000;117: 303S-17S. Review.

3. Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease:Oxidative Stress Study Group. Am.J Respir Crit Care Med 1997; 156:341-357.

4. Buhl R, Meyer A, Vogelmeier C. Oxidant-protease interaction in the lung - prospects for antioxidant therapy. Chest 1996; 110:1-9.

5. Cantin AM, North SL, Hubbard RC, Crystal RG. Normal alveolar epithelial lining fluid contains high levels of glutathione. J. Appl. Physiol. 1987; 63:152-7.

6. Cantin AM, Hubbard RC, Crystal RG. Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis 1989; 139:370-372.

7. Lothian B, Grey V, Kimoff RJ, Lands LC. Treatment of obstructive airway disease with a cysteine donor protein supplement. A case report. Chest 2000; 117:914-916.

8. Gillisen A, Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med 1998; 92:609-623.

9. Lands LC, Grey VL, Smountas AA. Effect of supplementation with a cysteine donor on muscular performance. J Appl Physiol 87:1381-5, 1999.


Accepted for publication in “Chest”

 Treatment Of Obstructive Airway Disease With A Cysteine Donor Protein Supplement: A Case Report

Bryce Lothian, MD*, Vijaylaxmi Grey, PhD*†, R. John Kimoff, MD‡, Larry Lands, MD, PhD*§

*Department of Pediatrics, †Department of Biochemistry, §Division of Respiratory Medicine, McGill University Health Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada

‡Division of Respiratory Medicine, McGill University Health Centre-Royal Victoria Hospita, Montreal, Quebec, Canada

ABSTRACT: Oxidant/antioxidant imbalance can occur in obstructive airways disease, as a result of ongoing inflammation.  Glutathione plays a major role in pulmonary antioxidant protection.  As an alternative or complement to anti-inflammatory therapy, augmenting antioxidant protection could diminish the effects of inflammation.  We describe a case of a patient with obstructive lung disease, responsive to corticosteroids, with low whole blood glutathione levels.  Following one month of supplementation with a whey-based oral supplement, designed to provide glutathione precursors, whole blood glutathione levels and pulmonary function significantly and dramatically increased.  The potential for such supplementation in pulmonary inflammatory conditions deserves further study.


Journal of Cystic Fibrosis,  Vol 2, Issue 4, December 2003

 Improved Glutathione Status in Young Adult Patients with Cystic Fibrosis Supplemented with Whey Protein

V Greya, SR Mohammedb, AA Smountasb, R Bahloolb, LC Landsb

aThe Department of Pathology and Molecular Medicine, McMaster Division, Hamilton Health Sciences, Hamilton, Ontario, Canada

bThe Department of Respiratory Medicine, McGill University Medical Center, Montreal Children’s Hospital,Montreal, Quebec, H3H 1P3, Canada

ABSTRACT – Background: The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the lung. This increased demand for glutathione (GSH) in cystic fibrosis may be limiting if nutritional status is compromised. We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein. Methods: Twenty-one patients who were in stable condition were randomly assigned to take a whey protein isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were compared with nutritional status and lung parameters. Results: At baseline there were no significant differences in age, height, weight, percent ideal body weight or percent body fat. Lymphocyte GSH was similar in the two groups. After supplementation, we observed a 46.6% increase from baseline (P<0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. Conclusion: The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress in the lung in cystic fibrosis.

  

Med. Sci. Sports Exerc., Vol. 37, No. 9, pp. 1468-1473, 2005.

 Effects of Cysteine Donor Supplementation on Exercise-induced Bronchoconstriction

JM Baumann, KW Rundell, TM Evans, AM Levine

American College of Sports Medicine. Marywood University, Human Performance Laboratory, Scranton, PA

ABSTRACT – Purpose: Reactive oxygen/nitrogen species (ROS/RNS) in resident airway cells may be important in bronchoconstriction following exercise. Glutathione (GSH) is a major lung antioxidant and could influence pathological outcomes in individuals with exercise-induced bronchoconstriction (EIB). This study examined the effects of supplementation with undenatured whey protein (UWP) in subjects exhibiting airway narrowing following eucapnic voluntary hyperventilation (EVH), a surrogate challenge for diagnosis of EIB. UWP is a cysteine donor that augments GSH production. Methods: In a randomized, double-blind, placebo-controlled study, 18 EIB-positive subjects (age: 25.2 ± 9.01 yr; weight: 77.3 ± 18.92 kg; height: 1.7 ± 0.09 m) with post-EVH falls of ³ 10% in FEV received 30 g UWP (TX) or casein placebo (PL)/d. Subjects performed 6-min EVH challenges before and after 4 and 8 wk of supplementation. Exhaled nitric oxide (eNO) was measured serially before spirometry and at 1-wk intervals. Spirometry was performed pre- and 5, 10, and 15 min postchallenge. Results: Subjects exhibited significant mean improvement in postchallenge falls in FEB from 0 wk (-2.6 ± 12.22%) with TX at 4 (-18.9 ± 12.89%, P<0.05) and 8 wk (-16.98 ± 11.61%, P< 0.05) and significant mean reduction in post-EVH peak falls in FEF from 0 wk (-40.6 ± 15.28%) with TX at 4 (-33.1 ± 17.11%, P <0.01) and 8 (-29.7 ± 17.42%, P<0.05) wk. No changes in FEV or FEF were observed in the PL group at any time point. Mean eNO for PL and TX groups at 0, 4, and 8 wk (46.8 ± 31.33, 46.5 ± 35.73, 49.3 ± 37.12 vs 35.2 ± 26.87, 29.1 ± 17.26, 34.7 ± 21.11 ppb, respectively) was not significantly different.

Conclusions: UWP may augment pulmonary antioxidant capacity and be therapeutically beneficial in individuals exhibiting EIB, as postchallenge pulmonary function improved with supplementation. The lack of significant change in eNO suggests that the pulmonary function improvements from UWP supplementation are independent of eNO

  

 Treatment Of Obstructive Airway Disease With A Cysteine Donor Protein Supplement: A Case Report

Bryce Lothian, MD*, Vijaylaxmi Grey, PhD*†, R. John Kimoff, MD‡, Larry Lands, MD, PhD*§

*Department of Pediatrics, †Department of Biochemistry, §Division of Respiratory Medicine, McGill University Health Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada 

‡Division of Respiratory Medicine, McGill University Health Centre-Royal Victoria Hospita, Montreal, Quebec, Canada

ABSTRACT:Oxidant/antioxidant imbalance can occur in obstructive airways disease, as a result of ongoing inflammation.  Glutathione plays a major role in pulmonary antioxidant protection.  As an alternative or complement to anti-inflammatory therapy, augmenting antioxidant protection could diminish the effects of inflammation.  We describe a case of a patient with obstructive lung disease, responsive to corticosteroids, with low whole blood glutathione levels.  Following one month of supplementation with a whey-based oral supplement, designed to provide glutathione precursors, whole blood glutathione levels and pulmonary function significantly and dramatically increased.  The potential for such supplementation in pulmonary inflammatory conditions deserves further study.

Glutathione: in defense of the lung.
Kelly FJ.
[Food Chemistry Toxicology. 1999; volume 37, number 9-10, pages 963-966.] Oxidative stress is implicated in the pathology of numerous diseases of the lung. These include cystic fibrosis, chronic obstructive airway disease and asthma. The lung, like many other tissues, has a range of antioxidant defences which help to maintain a balanced redox status. These antioxidants are present in the intracellular, the vascular and extracellular respiratory tract lining fluid (RTLF) compartments. The reduced glutathione (GSH) content of RTLF is particularly high and new findings are beginning to reveal the role that the RTLF GSH pool plays in defending the lung.

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis
Roum, James H., Zea Borok, Noel G. McElvaney, George J. Grimes, Allan D. Bokser, Roland Buhl and Ronald G. Crystal. [Journal of Applied Physiology 1999 Jul;87(1):438-43] Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered to 7 individuals with CF. ELF total, reduced and oxidized glutathione increased suggesting adequate RES delivery and utilization of GSH. PMA-stimulated superoxide anion (O2.) release by ELF inflammatory cells decreased after GSH therapy. This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2. release. No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF, and support the rationale for further clinical evaluation.

Systemic deficiency of glutathione in cystic fibrosis
Roum JH, Buhl R, McElvaney NG, Borok Z, Crystal RG. [J Appl Physiol 1993 Dec;75(6):2419-24] One process contributing to the airway derangement is the chronic burden of oxidants released by inflammatory cells on the respiratory epithelial surface. With this background, we hypothesized that glutathione in respiratory epithelial lining fluid (ELF) in CF patients might be oxidized and/or diminished in amount compared with that in normal subjects. As predicted, ELF in CF patients was characterized by a deficiency of glutathione, but this was secondary to a reduction in reduced glutathione. Unexpectedly, there was also a marked deficiency of reduced glutathione in plasma; i.e., the glutathione "deficiency" observed in ELF in CF patients is not limited to the site of the inflammation but is systemic. Although the etiology of this generalized deficiency of extracellular glutathione is unknown, it is important in considering options for treating the concomitant and devastating lung pathology in this disorder.

Lymphocyte glutathione levels in children with cystic fibrosis
Lands LC, Grey V, Smountas AA, Kramer VG, McKenna D. [Chest 1999 Jul;116(1):201-5] Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid.... lymphocyte GSH reflects lung GSH concentrations, .....the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress ....correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism....the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors.

Erythrocytic glutathione in cystic fibrosis. A possible marker of pulmonary dysfunction
Mangione S, Patel DD, Levin BR, Fiel SB. [Chest 1994 May;105(5):1470-3] We chose patients with CF because this disease is characterized by severe bronchial inflammation and marked oxidant-antioxidant imbalance. Although the GSH concentration of the two study groups was not significantly different, the RBC GSH concentration of patients with CF had a greater variability and was also inversely and significantly correlated to tests of pulmonary function. These data indicate a large and significant interindividual variability of erythrocytic antioxidants in patients with CF, with a compensatory, but probably inadequate, increase in patients with more severe respiratory deterioration. Red blood cell GSH concentration may thus provide a biologic marker for disease severity and a rationale for antioxidant manipulation in these patients.

Oxidative stress and regulation of glutathione in lung inflammation
Rahman I, MacNee W. [Eur Respir J. 2000 Sep;16(3):534-54.]
Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

Treatment of obstructive airway disease with a cysteine donor protein supplement: a case report
Lothian B, Grey V, Kimoff RJ, Lands LC. Department of Pediatrics, McGill University Health Centre-Montreal Children's Hospital, Montreal, Quebec, Canada.[Chest 2000 Mar;117(3):914-6] Case Study of a patient with Chronic Obstructive Pulmonary Disorder (COPD) - Oxidant/ antioxidant imbalance can occur in obstructive airways disease as a result of ongoing inflammation. Glutathione (GSH) plays a major role in pulmonary antioxidant protection. As an alternative or complement to anti-inflammatory therapy, augmenting antioxidant protection could diminish the effects of inflammation. We describe a case of a patient who had obstructive lung disease responsive to corticosteroids, and low whole blood GSH levels. After 1 month of supplementation with a whey-based oral supplement designed to provide GSH precursors, whole blood GSH levels and pulmonary function increased significantly and dramatically. The potential for such supplementation in pulmonary inflammatory conditions deserves further study.

Evidence of a defective thiol status of alveolar macrophages from COPD patients and smokers. Chronic obstructive pulmonary disease
Tager M, Piecyk A, Kohnlein T, Thiel U, Ansorge S, Welte T. [Free Radic Biol Med 2000 Dec;29(11):1160-5] In increasing numbers of pulmonary diseases an association with a loss of intracellular thiols, mainly glutathione, is postulated. Therefore, the quantitative measurement of thiols within different viable cells is a possible metabolic parameter for cellular function and defense capacity of all pulmonary immune cells including alveolar macrophages (AM), that are highly compromised by oxidative stress. AM obtained from bronchoalveolar lavage (BAL) of smokers and patients with chronic obstructive pulmonary disease (COPD) showed a significant thiol deficiency compared to a nonsmoker/non-COPD group. Lowest thiol concentrations (47% of control) were detected within the smoker(+)/COPD(+) group. This intracellular thiol deficiency significantly correlated with reduced lung function. With regard to the tightly regulated thiol metabolism of immune cells, these results imply the onset of functional disturbances in thiol deficient AM.

Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema
Engelen MP, Schols AM, and others. [Am J Respir Crit Care Med 2000 Jan;161(1):98-103.] "Chronic obstructive pulmonary disease (COPD) is often characterized by an impaired skeletal muscle energy metabolism, which is at least partly related to chronic hypoxia and a reduced diffusing capacity. This study illustrates that reduced glutamate levels in skeletal muscle of patients with emphysema are possibly related to an enhanced glycolytic activity and associated with decreased glutathione levels."

Frequent paracetamol use and asthma in adults
Shaheen SO, Sterne JA, Songhurst CE, Burney PG. [Thorax 2000 Apr;55(4):266-70] BACKGROUND: The pulmonary antioxidant glutathione may limit airway inflammation in asthma. Since paracetamol (acetaminophen) depletes the lung of glutathione in animals, a study was undertaken to investigate whether frequent use in humans was associated with asthma....RESULTS: Paracetamol use was positively associated with asthma...amongst cases increasing paracetamol use was associated with more severe disease. Frequent paracetamol use was positively associated with rhinitis, but aspirin use was not. CONCLUSIONS: Frequent use of paracetamol may contribute to asthma morbidity and rhinitis in adults.

Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart- lung transplantation
Behr J, Maier K and others. [Transplantation 2000 May 15;69(9):1856-60.] "Reduced glutathione was positively correlated with forced expiratory volume... We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder."

The effects of chronic alcohol abuse on pulmonary glutathione homeostatis
Moss M, Guidot DM, and others. [Am J Respir Crit Care Med 2000 Feb;161(2 Pt 1):414-9.] "This is the first report that chronic alcohol abuse alters glutathione homeostasis in the human lung, and suggests a potential mechanism by which chronic alcohol abuse predisposes susceptible patients to develop ARDS (acute respiratory distress syndrome). Recently, we determined that chronic ethanol ingestion in rats decreased the alveolar epithelial lining fluid (ELF) concentration of the antioxidant glutathione (GSH), which is a characteristic finding in patients with ARDS. However, the effects of chronic alcohol abuse on the human alveolar epithelium are essentially unknown.

Characterization of N-acetylcysteine and ambroxol in antioxidant therapy
Gillissen A and Nowak D. [Respir Med 1998 Apr;92(4):609-23.] "This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol." Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach.

Does N-acetyl-L-cysteine influence cytokine response during early human septic shock?
Spapen H, Zhang HB, and others. [Chest 1998 Jun;113(6):1616-24.] In this small cohort of patients with early septic shock, short-term IV infusion of NAC was well-tolerated, improved respiratory function, and shortened ICU stay in survivors. The attenuated production of IL-8, a potential mediator of septic lung injury, may have contributed to the lung-protective effects of NAC.

GSH: Allergies and Lung Protection

The risk of developing respiratory allergies from exposure to diesel emissions depends largely on genetics, according to a study funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

Researchers from the Keck School of Medicine of the University of Southern California and the David Geffen School of Medicine at UCLA have found that genetic characteristics seen in about half the population leave allergy-sufferers particularly susceptible to the effects of diesel particles.

Here are the relevant findings from the study:
 

► People with a certain genetic makeup are more susceptible to allergies caused by diesel engine exhaust.

► Antioxidants can detoxify these particles and temper the body's allergic inflammatory response. The better the body can use antioxidants to defend itself, the better it may protect itself from airborne pollutants.

► The enzymes glutathione S-transferase M1, or GSTM1, and glutathione S-transferase P1, or GSTP1 - that metabolize reactive oxygen species and detoxify chemicals present in diesel exhaust - were studied for their role in protecting the lungs.

► GSTM1 occurs in two common forms in the population-either "present" or "null." People born with two of the null form of the gene cannot produce the GSTM1 protective enzyme at all.

► The GSTP1 gene can occur with a common variation called ile105. People born with two of the ile105 form of the gene produce a less-effective form of the GSTP1 enzyme.

► People who lack the GSTM1 enzyme exhibit a larger allergic response than others. Also, those who lack GSTM1 and have at least one GSTP1 ile105 genetic variant show an even larger allergic response to diesel exhaust particles.

► The findings suggest that people who lack the genes to make key antioxidants may have difficulty fighting the harmful effects of air pollution.

► Up to 50 percent of the United States population could be in jeopardy of experiencing health problems related to air pollution because of these genetic variations.

► Overcoming this genetic deficiency could possibly be accomplished by either giving people drugs that replace the role of the genes or by boosting the body's natural defenses.

► Antioxidants may prevent the effects that air pollution have on allergic inflammation.

The research shows that boosting levels of antioxidants, especially the Master Antioxidant, Glutathione, may prevent the effects that air pollution have on allergic inflammation.
The best way to increase and maintain one's own Glutathione (GSH) levels is to include the excellent whole food supplement, Immunocal, to the diet. Immunocal contains all the amino acids needed by the body to synthesize intracellular Glutathione, naturally. It also has a patent for Improving the Immune Response, and will thus strengthen the Immune System of the host. (Go to main page to order)


The Original Article from the Lancet:
Effect of glutathione-S- transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study
F Gilliland et al. [The Lancet; 363 (9403): 119-25 (2004)]


Clin Exp Allergy. 1996 Jul;26(7):838-47

Reduced platelet glutathione peroxidase activity and serum selenium concentration in atopic asthmatic patients.

Misso NL, Powers KA, Gillon RL, Stewart GA, Thompson PJ.

Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Australia.

BACKGROUND: Asthmatic inflammation results in increased oxygen free radical generation and assessment of the activity of the selenium (Se) dependent anti-oxidant enzyme, glutathione peroxidase (GSH-Px) in asthma may therefore be important. OBJECTIVE: To test the hypothesis that reduced GSH-Px activity and Se intake contribute to asthmatic inflammation, platelet and whole blood GSH-Px activities and serum and whole blood Se concentrations were measured and compared in atopic and non-atopic asthmatic patients and non-asthmatic control subjects. METHODS: GSH-Px activities of whole blood and isolated platelets were assessed in 41 asthmatic patients (33 atopic) and 41 age- and sex-matched non-asthmatic subjects (15 atopic) by spectrophotometric assay based on the oxidation of NADPH. Se concentrations were determined by semi-automated fluorimetric assay. RESULTS: Mean (+/-SD) platelet GSH-Px activity was lower in asthmatic (89.5 +/- 45.7 mumol NADPH oxidized min-1 g-1 of protein) than in non-asthmatic subjects (109.9 +/- 41.9; P = 0.038) and in atopic (89.7 +/- 45.1, n = 48) compared with non-atopic subjects (113.7 +/- 40.9, n = 34; P = 0.016). Mean whole blood GSH-Px activity was also lower in atopic (12.2 +/- 5.2 mumol NADPH oxidized min-1 g-1 of Hb) than in non-atopic subjects (14.5 +/- 4.2; P = 0.038). In non-asthmatic subjects, the mean whole blood GSH-Px activity was lower in men (9.9 +/- 3.5) than in women (14.5 +/- 3.7; P = 0.0004) and was positively correlated with age (r = 0.51; P = 0.0006). Mean serum Se was lower in asthmatic (1.07 +/- 0.12 mumol/L) than in non-asthmatic subjects (1.16 +/- 0.31; P = 0.036). Using multiple linear regression, asthma was an independent predictor of decreased platelet GSH-Px after gender, age and serum Se were taken into account (P = 0.048) while atopy was a significant predictor of low whole blood GSH-Px independent of asthma, gender, age and whole blood Se (P = 0.033). CONCLUSIONS: In addition to Se status, atopy, gender and age all appear to influence GSH-Px activity, although the relative importance of these factors may differ in asthmatic and non-asthmatic populations. It seems likely that the reduced activity of this enzyme in platelets and blood may reflect mechanisms associated with the pathogenesis and severity of asthma.

PMID: 8842559 [PubMed - indexed for MEDLINE]


Clin Chim Acta. 2001 Mar;305(1-2):107-14.

Excessive free radical generation in the blood of children suffering from asthma.

Shanmugasundaram KR, Kumar SS, Rajajee S.

Department of Medical Biochemistry, Dr. A.L.M.P.G. Institute of Basic Medical Sciences, University of Madras, Taramani Campus, - 600 113, Chennai, India. erbs@satyam.net.in

The aim of the present study is to evaluate the biochemical parameters in blood relevant to oxygen free radicals and antioxidant defenses in children with asthma. A total of 210 asthmatic children, aged 5-18 years, were studied at two different times, once during a severe episode of wheeze (during episode category) and the other after recovery (resting condition). A total of 180 healthy children participated in the study as age and sex matched healthy controls. Superoxide and hydroxyl radical assays were used as a measure of free radical formation. Antioxidant enzymes and free radical scavengers in blood were also assayed. Lipid peroxidation products were assayed in plasma and erythrocytes to evaluate the imbalance (if any) between oxidant (radical) formation and their inactivation. Serum IgE concentrations and peak expiratory flow rate (PEFR) were used as measures of allergic reactions and residual lung capacity, respectively. Excessive production of superoxide and hydroxyl radicals were noted in the blood cells in asthmatics and were correlated to the severity of disease measured as PEFR. Superoxide dismutase and free radical scavengers in blood were significantly lower in asthma, even during resting condition. The present observations endorse the correlation between disease severity and oxygen radical production in asthma subjects. Oxygen metabolites may play a direct or indirect role in the modulation of airway inflammation. Excessive superoxide and hydroxyl radical production may be used as a marker for susceptibility to asthma and for monitoring therapeutic measures.

PMID: 11249929 [PubMed - indexed for MEDLINE]

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