A study of the antioxidant status in Maltese patients suffering from bronchial asthma

Abstract

Asthma is an inflammatory condition in which several mediators interact to bring about a narrowing of the airways. During such an inflammatory reaction, eosinophils, monocytes, macrophages, lymphocytes and neutrophils all release reactive oxygen species. A free radical cascade ensues, producing a variety of oxidative products, main amongst which are superoxide, hydrogen peroxide, hydroxyl radicals and a range of organic hydroperoxides. These species are known to induce smooth muscle contraction, damage the respiratory epithelium, stimulate arachidonic acid metabolism and enhance the degree of airway hyperresponsiveness (Kanazawa et al., 1991). Defence against this destructive potential is afforded by an array of antioxidants, whose role, is to provide a route for the detoxification of these highly reactive moieties. Superoxide dismutase is responsible for the dismutation of the superoxide ion to hydrogen peroxide, while selenium-dependent glutathione peroxidases catalyse the reduction of hydrogen peroxide and organic hydroperoxides. These enzymes therefore play a pivotal role in modulating the damaging effect of reactive oxygen species on the airways. Based on these considerations, this study aimed to establish the antioxidant status of Maltese patients suffering from bronchial asthma, and to compare it to baseline values obtained from healthy controls. The study also investigated the effects which inhaled and oral glucocorticoid therapy may have on these defence systems. Plasma selenium, erythrocyte glutathione peroxidase, plasma glutathione peroxidase and erythrocyte superoxide dismutase, were measured in mild and severe asthmatics, as well as healthy controls. All patients also underwent spirometry. Blood sampling and pulmonary function testing were always carried out between 9. 00 am and 11. 00 am, in order to eliminate possible diurnal variation effects. In addition, the antioxidant profile of a group of 10 patients suffering from severe asthma was established prior to and after four weeks treatment with inhaled beclomethasone dipropionate (750μg b.d.). Similar investigations were carried out on 14 severe asthmatics prior to and after two weeks of oral prednisolone therapy (10-15 mg daily taken as a single morning dose). There were no gender or age dependent variations in any of the measured parameters in healthy volunteers. Plasma selenium levels were similar in both control (114.4 ± 3.5ng/ml, n = 49), mild asthmatic (116.4 ± 4.8ng/ml, n = 22) and severe asthmatic (114.0 ± 3.3ng/ml, n = 29) groups, (mean± SEM). However, a significant increase was observed in a group of severe asthmatics (n = 14) who were given oral prednisolone therapy, with mean levels rising from 115.7 ± 4.5ng/ml pre-treatment to 141.0 ± 4.4ng/ml afterwards (p < 0.005). Erythrocyte superoxide dismutase levels were significantly reduced in both mild (62.9 ± 2.9 SOD525U/ml, n = 22) and severe (60.6 ± 1.9 SOD525U/ml, n = 29) asthmatic patients, irrespective of therapy, when compared to control values ( 68. 5 ± 1.0 SOD525U/ml, n = 49) (p < 0.005). However, no changes were observed in either erythrocyte or plasma glutathione peroxidase. Administration of inhaled beclomethasone dipropionate did not exert any demonstrable effect on the antioxidant profile. Within the severe asthmatic group, plasma glutathione peroxidase was found to correlate with the degree of disease severity as quantified by FEV 1, PEF and FVC (p < 0.05). The same enzyme correlated with plasma selenium levels, within the control subject group (p < 0.05). The correlation of selenium with plasma glutathione peroxidase in control subjects, suggests a non-saturated selenium-dependent synthesis, or a selenium-dependent compartmentalisation of the enzyme. Correlation of the plasma enzyme with spirometric parameters within patients, might be the result of an oxidative stress dependent increased enzyme demand in the airways. This work appears to be the first to report the effects of low dose oral, as well as high dose inhaled glucocorticoids, on the antioxidant profile of patients suffering from bronchial asthma. Likewise, the correlation between plasma glutathione peroxidase and lung function parameters in severe asthmatics, does not appear to be stated in the literature.