Asthma: Oxidative Stress & Antioxidant Deficiencies
How Oxidative-Antioxidant Balance is Disturbed in Asthma
Asthma is characterized by reversible episodes of airway obstruction, combined with chronic inflammation of the lungs, which eventually can lead to remodeling of the airway wall.
Infiltration of inflammatory cells into the airways results in the formation of active oxygen and nitrogen species that impose an additional oxidative stress on the lungs of patients with asthma.
This oxidative stress is usually treated by a number of antioxidant defense mechanisms present in the lungs. However, the lungs of patients with asthma, increased oxidative stress and / or antioxidant defense deficiencies can lead to an imbalance that aggravates chronic inflammation and tissue damage.
Inflammatory cells in the airways in asthma, including eosinophils, neutrophils and macrophages, are a major source of active oxygen and nitrogen species that play an important role in the pathogenesis of asthma.
NADPH oxidase in these cells results in the production of anion superperoxide, leading non-enzymatically by catalysing the dismutase to H2O2. The oxidative effects of H2O2 are enhanced by neutrophils and eosinophils through the action of myeloperoxidase and eosinophil peroxidase, which catalyze the reaction of H2 O2 with Cl- to form hypochlorous acid and Br- to form hypobromonic acid.
Acquired inflammatory cells, as well as alveolar epithelial cells in the airways, are also responsible for the production of increased amounts of nitric oxide in the respiratory tract of asthmatic patients.
Although the exact mechanism for increasing nitric oxide and its role in the pathogenesis of asthma remains unclear, it is supposed that the production of nitric oxide under oxidative stress conditions results in the formation of reactive nitrogen species that form and / or enhance inflammation of the asthmatic airways.
Nitric oxide is oxidized to nitrites and nitrates and reacts rapidly with eosinophil-derived peroxide to form the potent oxidase of peroxynitrite and these reaction products can be responsible for most of the nitric oxide nitrate effects.
Eosinophilic peroxidase is also responsible for the formation of oxidants, such as hypobromotic acid in patients with asthma.
Oxidative stress can also occur in the lungs of patients with asthma as a consequence of altered expression and activity of antioxidant enzymes that play a vital role in protecting lung tissue from the toxic effects of ROS.
Antioxidant Deficiency & Asthma
A glutathione deficiency, which catalyzes the reduction of H2O2 and lipid hydroperoxides, was first observed in platelets of patients with native and aspirin-sensitive asthma.
This finding was confirmed in platelets as well as in erythrocytes and leukocytes in both atopic and non-atopic asthma patients.
Reduced glutathione activity in asthmatic patients may be associated with low selenium levels.
Low vitamin C intake has also been associated with increased bronchial reactivity, wheezing symptoms in adults and children, as well as coughing and wheezing in new smokers.
Other recent studies have shown that asthmatic patients have lower vitamin C intake than non-asthmatics, and that vitamin C intake was particularly low in subjects with severe asthma.
According to these reports of low vitamin C intake in asthmatic patients, plasma concentrations of vitamin C are found to be lower in asthma patients, particularly in patients with severe asthma and in the fluid lining of the lung, while in sputum concentrations of vitamin C are also low in patients with mild asthma.
As an integral component of the glutathione peroxidase enzyme, selenium (Se) plays an important role in the antioxidant defense system. Studies from the United Kingdom, New Zealand and Australia have identified deficiencies in serum levels of blood in asthmatic patients.
Flavonoids, a subgroup of a wide variety of polyphenolic antioxidant compounds composed of plants. In a large study of approximately 10,000 Finnish adults, there was a significant reversed correlation between flavonoid uptake and asthma incidence. Additionally, this reverse correlation was also observed in a UK study, and attributed to a possible protective antioxidant action of flavonoids.
Glutathione is an important antioxidant in the lung and is present in higher concentrations in the fluid epithelial lining of the lung than in the blood.
Glutathione has also been implicated in the mechanism by which frequent consumption of paracetamol may be associated with an increased risk of developing asthma. Paracetamol can destroy the reduced glutathione in the lungs, as well as the total antioxidant capacity of the serum, resulting in increased sensitivity to oxidative stress.
A study of short-term supplementation with vitamin C showed reduced bronchial reactivity in asthmatic subjects, while supplementation with vitamin C resulted in a significant protective effect on lung function in road workers exposed to high ozone concentrations in the city of Mexico and in the same city; supplementation with vitamin C reduced the adverse effect of exposure to ozone in the airways of children with asthma.
Similarly, short-term supplementation with vitamin C provided partial protection against acute effects of ozone in lung function, a group of Dutch cyclists, but also adults with asthma.
In the unique placebo-controlled, double-blind study of asthma supplementation in asthma, people with chronic naïve asthma were randomized to receive a daily selenium or placebo supplement for 14 weeks.
In subjects treated with Se, the activity of glutathione peroxidase increased relative to the placebo group and improved, as assessed by a compound result of some clinical and subjective outcomes.
In another study, supplementing with 200 μg / day Se for 96 weeks resulted in reduced use of inhaled and oral corticosteroids in asthmatic patients who depend on these drugs.
It is clear that the airways of patients with asthma have increased levels of oxidative stress due to the production of inflammatory cells and epithelial cells due to active oxygen and nitrogen species.
There are also growing signs of inadequacy in asthmatic patients of some of the key antioxidant enzymes, vitamins and small molecules, and this may be due to the disease process and / or nutritional alterations.
Therefore, the available evidence suggests that the oxidative / antioxidant balance is disturbed in asthma.