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Inhaled corticosteroids (ICS) are the standard of care in asthma and are widely used in the treatment of patients with COPD. The influence of steroids on inflammatory processes has long been established since glucocorticoids and their receptor belong to the regulatory network involved in inhibition of several inflammatory pathways. Inflammatory processes are usually accompanied by an increased oxidative burden followed by a depletion of antioxidants. Therefore, the effects of steroids on antioxidant status have been investigated revealing possible positive effects on the reduced antioxidant enzyme activity. Nevertheless, the mechanisms of this modulation have not been fully elucidated yet. It is possible that antioxidant enzyme activity is regulated at the level of transcription. Additionally, because of the fact that antioxidant enzymes are trace element dependent, steroids may affect their activity through influence on trace element accumulation. This review summarizes the effects of steroids on the antioxidant enzymes activity in vitro and in vivo in relation to asthma and COPD.

In order to develop efficient therapeutic regimes for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication which can suppress various pathogenic processes in this disease. Besides its well-known and efficient mucolytic action, NAC meets these needs by virtue of its antioxidant and anti-inflammatory modes of action. NAC is a thiol compound which by providing sulfhydryl groups, can act both as a precursor of reduced glutathione and as a direct ROS scavenger, hence regulating the redox status in the cells. In this way it can interfere with several signaling pathways that play a role in regulating apoptosis, angiogenesis, cell growth and arrest and inflammatory response. Overall, the antioxidant effects of NAC are well documented in in vivo and in vitro studies. It successfully inhibits oxidative stress at both high and low concentrations, under acute (in vitro) and chronic administration (in vivo). With regard to its anti-inflammatory action, in contrast, the effects of NAC differ in vivo and in vitro and are highly dose-dependent. In the in vitro settings anti-inflammatory effects are seen at high but not at low concentrations. On the other hand, some long-term effectiveness is reported in several in vivo studies even at low dosages. Increasing the dose seems to improve NAC bioavailability and may also consolidate some of its effects. In this way, the effects that are observed in the clinical and in vivo studies do not always reflect the success of the in vitro experiments. Furthermore, the results obtained with healthy volunteers do not always provide incontrovertible proof of its usefulness in COPD especially when number of exacerbations and changes in lung function are chosen as the primary outcomes. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives, because of their multiple molecular modes of action, remain promising medication once doses and route of administration are optimized.

Objective and Background: Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time-course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients., Methods: Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: alpha-tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured., Results: There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P<0.05). Alpha-tocopherol was the lowest 24 h after admission and increased significantly at discharge (P<0.05)., Conclusions: There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non-enzymatic antioxidants such as alpha-tocopherol.

Inhaled corticosteroids (ICS) are widely used for the treatment of COPD despite of controversial statements concerning their efficacy. The use of N-acetylcysteine (NAC), a mucolytic drug with antioxidant properties, is less clear, but it may counteract the oxidant-antioxidant imbalance in COPD. The aim of this study was to evaluate whether treatment of COPD patients with ICS or NAC is able to improve inflammatory indices and to enhance lung function. ICS treatment enhanced protective markers for oxidative stress such as glutathione peroxidase (GPx) (51.2 +/-5.8 vs. 62.2 +/-8.6 U/g Hb, P<0.02) and trolox-equivalent antioxidant capacity (TEAC) (1.44 +/-0.05 vs. 1.52 +/-0.06 mM, P<0.05). NAC decreased sputum eosinophil cationic protein (318 +/-73 vs. 163 +/-30 ng/ml, P<0.01) and sputum IL-8 (429 +/-80 vs. 347 +/-70 ng/ml, P<0.05). The increased antioxidant capacity prevented an up-regulation of adhesion molecules, since the levels of intracellular adhesion molecule 1 (ICAM-1) correlated negatively with GPx (P<0.0001) and TEAC (P<0.0001). On the other hand, expression of adhesion molecules was promoted by inflammation, reflected by a positive correlation between the levels of IL-8 and ICAM-1 (P<0.0001). The effects of treatment on lung function were only reflected in the FEV(1) values. The absolute value of FEV(1), both before and after salbutamol inhalation, increased from 1690 +/-98 to 1764 +/-110 ml, and 1818 +/-106 to 1906 +/-116 ml, respectively, after ICS (P<0.05) . Ten weeks after treatment, FEV(1) values dropped to 1716 +/-120 ml post-salbutamol (P<0.05). When followed by treatment with NAC, these values decreased even further to 1666 +/-84 ml. These results suggest that ICS improved lung function in COPD patients with moderate airflow obstruction, beside a minor improvement in the oxidant-antioxidant imbalance leading to a lesser expression of ICAM-1. Treatment with NAC decreased some inflammatory parameters and had indirectly an inhibitory effect on the expression of adhesion molecules.

Objective: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation., Methods: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure., Results: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure., Conclusion: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.

Background: Chronic obstructive pulmonary disease (COPD) is accompanied by both airway and systemic inflammation and by oxidative stress. This study aimed to characterise the relationship between oxidative stress and inflammatory components in induced sputum and blood., Material & Methods: We studied blood and sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at baseline (no treatment) and after 10 weeks treatment with either inhaled steroid, fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N-acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP, sICAM-1, NE) in sputum and serum and we compared them with blood markers of oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A)., Results: At baseline blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8 disappeared after NAC treatment. The correlation between sICAM and GPx disappeared after FP treatment. The correlation between TEAC and GPx was maintained after both NAC and FP., Conclusions: The relationship between markers of inflammation, adhesion and antioxidant capacity is significantly modulated by treatment with N-acetylcysteine or inhaled corticosteroids.