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Oxidative stress implicated in allergy and asthma
Researchers at the University of Texas Medical Branch at Galveston have found that in addition to an abnormal immune overreaction, another factor is necessary for a severe inflammatory allergic response or asthma subsequent to inhaling pollen. The factor is oxidative stress, damage caused by reactive oxygen species formed by interactions between an enzyme found in pollen and airway cells. The research was published in the August 2005 issue of the Journal of Clinical Investigation (http://www.jci.org/).
The researchers found that an enzyme in pollen and molds called NADPH oxidase produced reactive oxygen species in cell cultures and in the lungs and airways of mice. Oxidative stress rapidly led to the production of inflammatory immune signaling molecules and the accumulation of inflammatory cells that is typical of allergic reactions. When pollen extract from which NADPH oxidase had been removed was tested, no reactive oxygen species were formed, and there was a minimal increase in inflammatory immune cells. Lead author and University of Texas Medical Branch associate professor Istvan Boldogh explained, “"There has been a lot of discussion about oxidative stress exacerbating asthma and allergies, but this is the first direct evidence that oxidative stress is required to induce a robust inflammation, and the first demonstration that a source of that stress is right there in the pollen itself. We showed that you need both oxidative stress and antigenic exposure to get a robust allergy or asthma attack, and also that the first few minutes of the exposure are critical. The antigen exposure has to happen in parallel with oxidative stress, and having both components in the pollen makes that possible."
The authors hope that their finding will encourage efforts to discover pollen NADPH oxidase inhibitors or compounds that will help prevent oxidative stress in the lungs. Conflicting results obtained by studies utilizing vitamin C to reduce airway inflammation could be the result of insufficient levels of the vitamin in the lungs and airways due to rapid metabolism of antioxidants in these areas, leading to the suggestion that antioxidants could be delivered every couple hours via inhalation. Dr Boldogh added, "If we can find an antioxidant with a longer half-life, it could be really very effective in asthma and allergy treatment and also prevention.”
Allergies are abnormal immune reactions to specific agents known as antigens or allergens. Examples of common allergens are foods, drugs, pollens, dust mites, mold spores, animal dander, feathers, and insect venoms, as well as other substances which non-allergic people find relatively non-dangerous with usual exposure. Allergies may develop when an otherwise innocent substance has significant contact with an already inflamed surface (sensitization), such as from a viral infection or exposure to irritants, and becomes involved in the immune response. Thereafter, repeated exposure to such a substance may evoke an allergic response with the release of histamine and a variety of other pro-inflammatory substances, including enzymes, leukotrienes, and interleukins, and the creation of damaging free radicals. The multiplicity of these proinflammatory substances explains why single medications such as antihistamines often fail to completely control symptoms.
Vitamin E is a fat-soluble vitamin that acts as a free radical scavenger of lipids or fat, protecting cell membranes and preventing damage to membrane-associated enzymes. Leukotrienes (LT) are lipid membrane-derived compounds generated by the metabolism of arachidonic acid by the enzyme lipoxygenase found in leukocytes and other cells. In a manner somewhat analogous to histamine, leukotrienes have a number of undesirable allergic and inflammatory effects, including smooth muscle contraction; vasoconstriction; vasodilatation and increased blood vessel permeability; simulation of mucus secretion; and increased airway hyporeactivity.
Centanni et al. (2001) considered the role vitamin E plays in treating asthma and allergies by modifying the leukotriene pathway with vitamin E. Vitamin E in a concentration-dependent manner inhibited the receptor-mediated activation of neutrophils which, in an asthmatic, results in the synthesis of leukotrienes. The study indicated that vitamin E may suppress leukotriene pathways, making it potentially useful in the treatment of asthma/allergic patients.
A study by Hijazi et al. (2000) indicated lower levels of antioxidants such as vitamin E increased the risk of allergies by threefold. Allergic reactions can be mitigated and sometimes eliminated by maintaining high levels of antioxidants. The research of Dr. Linus Pauling, two-time Nobel Prize winner, has highlighted vitamin C as an essential water-soluble nutrient that acts as a free radical scavenger, enhances collagen synthesis, and boosts immune function. In particular, vitamin C is a natural antihistamine and may be taken at doses up to 12,000 mg or more daily, provided the dose is kept below the diarrhea level.
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