Several studies have revealed that oxidants-antioxidants balance is an essential factor for the normal physiological function of the lungs. An increased oxidant and/or decreased antioxidant may reverse the physiologic oxidant-antioxidant balance in favor of oxidants. Thus, oxidative stress plays an important role in the pathogenesis of asthma and oxidants caused lipid peroxidation by oxidizing fatty acids and polyunsaturated lipids of cell membranes.
The oxidant–antioxidant status was investigated in blood (red blood cell and plasma) because it is an easily available source and also considered as an important pool of antioxidant defenses in the body rather than BAL fluid which is obtained through an invasive bronchoscope technique.[35
] Furthermore, asthma is an inflammatory disease in which cells are recruited from the peripheral blood.
In this work, it has been observed that the asthmatic patients have increased oxidative stress. It was shown by remarkable increase in lipid peroxidation product (MDA) and protein carbonyls as well as decrease in protein sulfhydryls in plasma [Figure –]. These are accompanied by alterations in several endogenous enzymatic antioxidants in blood including decreased GPx and SOD activities. The distinguished changes were noticed in catalase activity of erythrocytes and total antioxidant power of plasma of asthmatic patients. Rahman et al
. reported that the plasma MDA level was higher in asthmatic patients than controls as well as in patients with asthma exacerbation as compared to stable asthma.[12
] Similarly, another study entails that MDA level in BAL fluid was higher in mild to moderate asthmatic patients.[20
] Moreover, protein carbonyl content was also significantly higher in asthmatic patients because most of the amino acids can be oxidized by ROS. Peroxynitrite anion is a potent oxidant that mediates not only the oxidation of both non-protein and protein sulfhydryls but also induces lipid peroxidation.[36
Several studies have demonstrated alterations in different endogenous antioxidants in patients with asthma. The alterations in antioxidant defenses may involve either an increase or a decrease depending on the changes occurring due to a defense response. SOD is an intracellular antioxidant enzyme, helping in removing superoxide anion. In some studies, it has been reported that SOD activity in airway epithelium and erythrocytes of asthmatic patients was lower than healthy controls.[17
] We have also noticed significantly lower activities of SOD and catalase in red blood cells [Figure ,] and these findings were very much similar to the earlier reported by Rai and Phadke (2006).[38
In a previous study, it has been reported that GPx play a significant role in peroxyl scavenging mechanism and maintaining functional integration of the cell membrane. Here, we observed a significant decrease in GPx activity in asthmatic patients as compared to controls , which led to the high elevation of lipid peroxidation products as reported in the same investigated samples. Lower GPx level in asthmatic patients can be related to the clinical presentation of the disease and it indicates the presence of H2
in breath condensate of exhaled air which is elevated in asthmatics patients.[37
] Decreased activity of GPx has been well documented in literature[39
] and it is in favor of our findings. Selenium is an essential component of GPx and it indirectly helps in protecting cells against damage caused by free radicals. This might arise as a result of deficiency of selenium or inactivation caused by OH·
] A number of studies have been done to measure the selenium deficiency in asthma through the antioxidant effects of GPx and it has been found that plasma levels of selenium was significantly lower in asthmatic patients.[42
] GPx is essential for removing toxic lipid oxidation products and H2
, which are continuously generated as a result of sequestration and infiltration of inflammatory leukocytes in the lung. Low SOD activity together with low GPx activity in asthmatic patients proved the contribution of oxidative stress in the etiology of asthma. It was reported that the glutathione system is altered in lung inflammatory conditions such as asthma and many reports have shown that alterations in glutathione level have been found in asthmatic airways.[45
The present finding of our study also shows that the asthmatic patients have significantly higher level of total blood glutathione as compared to control subjects . Mak et al
. have also reported that the total glutathione level increased in erythrocytes of asthmatic individuals.[46
] There have been several reports on the decreased antioxidant capacity in asthmatic patients with intense oxidative load. In this study, we found very low total antioxidant status  which is correlated to the findings reported by Rahman et al
The present study also demonstrates that the measures of oxidative stress and antioxidants differ significantly between patients grouped according to severity of asthma except SOD . It revealed that severe persistent asthmatics have highest levels of plasma lipid peroxidation products and simultaneously lowest level of plasma antioxidants. An increasing trend was observed in the level of MDA, total protein carbonyls, and total blood glutathione among patients with intermittent to severe asthma while total protein sulfhydryls, enzymatic antioxidants, and total antioxidant capacity shows a decreasing pattern in these respect (P
< 0.05). We have also observed a dramatic enhancement in catalase activity among asthmatic patients (intermittent to severe). Al-Abdulla et al
. also reported that the mean serum level of MDA was significantly raised with increasing severity of asthmatic attack among patients grouped according to degree of severity.[47
] Previously, Kanazawa et al
. have also found differences related to severity in patients with acute exacerbations.[48
] The association between asthma severity and anthropometric measurement demonstrates that age and gender was unrelated to disease severity similar to our findings.[49
] Our results are also of interest in the context of increased oxidative burden remarkably associated to the pulmonary airways obstruction . Markers of lipid peroxidation (TBARS), total protein carbonyls, and total blood glutathione level showed negative associations with FEV1 (% predicted). Furthermore, it was also noticed that total antioxidant status, erythrocyte GPx, and total protein sulfhydryls were positively associated with FEV1 (% predicted). Schunemann et al
. found a remarkable negative correlation between plasma TBARS and red cell GSH, but they did not find any significant correlation with GPx and total antioxidant status.[50
] A negative association in erythrocyte SOD activity was also observed, but this was not significant. Wood and co-workers also reported that SOD activity was negatively associated with the severity of asthma.[30
] Some workers also demonstrated that the superoxide anion release was greater in patients with exacerbation of their disease and it was also inversely correlated with FEV1.[48
] It suggested that the lower antioxidant defense cause greater degree of airway obstruction (decreased FEV1 % predicted).
In conclusion, this work describes the role of oxidative stress and antioxidants in severity of disease which provides a strong evidence for oxidant-antioxidant imbalance in disease progression. The findings of this study further strengthen the evidence that the altered oxidant-antioxidant balance is associated with airways obstruction. In further studies, we realized the need to elucidate pathophysiological mechanism involved in lung injury related to oxidant-antioxidant imbalance.