Track topics on Twitter Track topics that are important to you
To study the effects of 1200mg gamma tocopherol (yT), a form of vitamin E, given daily on the response of the airway in mild asthmatics after exposure to ozone (O3)
Allergic asthma (AA) is the most commonly encountered respiratory disease in children and adults in the United States and is a leading cause of morbidity worldwide. Among the most disruptive expressions of disease in AA is acute asthma exacerbation. The CDC lists ambient air pollutants and environmental tobacco smoke as among the most common triggers for acute asthma exacerbation. Ozone (O3) is the most commonly encountered ambient air pollutant in the US.
Increased oxidative stress and decreased antioxidant capability have been observed in asthmatics. These pollutants are pro-inflammatory and are associated with increased oxidative stress, which would exacerbate reactive oxygen and reactive nitrogen species (ROS and RNS)-induced injury in asthmatics. O3 injures epithelial cells, releasing secondary mediators which activate inflammatory cells, in part by ligation of TLR4, the primary receptor for LPS. TLR4 activation of inflammatory cells activates NF-kB and induces oxidative stress. O3 and LPS has been associated with exacerbation of asthma, and we have reported that O3 and LPS augments allergic airway inflammation in allergic asthmatics (AA). Development of interventions to mitigate these responses will greatly decrease disease morbidity. Given the role that oxidants play in the pathophysiology of asthma exacerbation, defects in antioxidant levels would increase risk for acute asthma exacerbation. Nutritional deficiencies in vitamin E, ascorbate and selenium have been linked to asthma severity, and asthmatics have decreased antioxidant levels in airway fluid. It has been shown that vitamins C and E are decreased in airway fluids of asthmatics. Additionally, genetic factors may increase risk for oxidant induced exacerbation of asthma. Many investigators have reported that persons who are homozygous for the null polymorphism of the Glutathione-S-Transferase Mu1 (GSTM1) gene and unable to produce GSTM1 protein (the GSTM1 null genotype) have increased risk of acute pollutant-induced exacerbation of asthma. This lab has shown in healthy volunteers that the GSTM1 null genotype is associated with increased inflammatory response to O3, with no impact on the nociceptive response to this pollutant.
Other researchers have shown that the GSTM1 null genotype is associated with increased response to secondhand tobacco smoke, diesel exhaust, and other particulate matter components. Romieu et al demonstrated that children with asthma in Mexico City were had increases susceptibility to O3-induced exacerbations if they had the GSTM1 null genotype. This group also found that GSTM1 null AAs selectively benefited from antioxidant intervention. The GSTM1 null genotype is found in 20-40% of the population, and may be overrepresented in allergic populations. Taken together, these observations show that the sizable GSTM1 null population is at risk for pollutant-induced airway disease, and that antioxidant intervention targeting the action of ROS and RNS will benefit asthmatics and especially GSTM1 null asthmatics.
A non-exclusive list of proposed antioxidants includes radical scavengers such as ascorbate, a-tocopherol (aT), y-tocopherol (yT) or inducers of NRF2, which activate NRF2 with subsequent broad upregulation of acute phase II and antioxidant proteins. These agents are available in naturally occurring foods and as nutritional supplements. A number of animal, cell culture and epidemiological studies support the idea that antioxidant supplementation is useful in allergic airway disease. However, despite these studies and widespread public and scientific enthusiasm regarding use of such agents in asthmatics, there are scant human data to support or refute the use of such interventions for either acute or chronic allergic airways disease.
Gamma tocopherol has both radical scavenging and anti-inflammatory actions which may play important roles in decreasing pollutant-induced and allergic injury to the airway. Like other isoforms of vitamin E, yT is a potent ROS scavenger and is also a powerful nucleophile that traps electrophiles such as peroxynitite in lipophilic compartments. One mechanism by which y-T is cytoprotective is scavenging of RNS at the un-substituted C-5 position on the hydroxy-chroman ring of y-T to form 5-NO-y-tocopherol (5-NO-yT). Overall, vitamin E provides general protection of DNA, lipids and proteins from radical stress. An example of such protection is shown in rodent studies of prostate cancer in which intake of yT is associated with decreased DNA methylation of CpG rich regions of the NRF2. NRF2 is a master regulator of numerous cytoprotective antioxidant enzymes.
Supplementation with yT also prevents protein nitration and attenuates loss of plasma vitamin C in plasma in a rodent peritonitis model of inflammation. Our group has also shown that yT inhibits COX-2 and 5-LO in LPS-stimulated macrophages and IL-1b stimulated epithelial cells. These actions are mediated primarily by the yT metabolite 2, 7, 8-trimethyl-2S-(.-carboxyethyl)-6-hydroxychroman (y-CEHC) which requires hydroxylation of the y-methyl group of yT by cytochrome P450 (CYP450). In carrageenan- induced inflammation in male Wistar rats, yT decreases prostaglandin (PGE2) and leukotriene (LTB4) production, suggesting that LO-mediated production of leukotrienes may also be inhibited by yT. Tocopherols, including yT, also modulate gene expression of a number of inflammatory genes. Thus, yT and other tocopherols decrease production of a number of pro-inflammatory cytokines at the transcriptional level.
In animals, it has also been shown that gamma tocopherol reduces baseline eosinophilia in the airway. In our early phase I studies of gamma tocopherol-enriched mixed tocopherols (gT-mT) we have shown that gT-mT inhibits monocyte induced cytokine production, decreases baseline nitrosative stress, and inhibits LPS eosinophil and neutrophil influx in healthy volunteers.
There is widespread opinion that antioxidant nutrients like gamma tocopherol ( yT, a form of Vitamin E) are an untapped and inexpensive intervention for environmentally triggered acute asthma. However, there is a crucial gap in evidence-based support of such interventions in asthma. A lack of coordinated research assessing specific antioxidant regimens from preclinical, phase I and phase II studies impedes development of phase III antioxidant trials in asthmatic populations. It is also unclear which physiological endpoints are most relevant in such studies.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
gamma tocopherol, Placebo
Center for Environmental Medicine, Asthma and Lung Biology
Not yet recruiting
University of North Carolina, Chapel Hill
Published on BioPortfolio: 2016-09-22T20:53:25-0400
To evaluate serum levels of gamma tocopherol and it's metabolites after 3 doses, each separated by 12 hours.
Purpose: This is a non-masked study with a primary endpoint of in vitro basophil activation by the allergen D. farinae, comparing basophil activation before and after seven days of supple...
Asthma is a common respiratory disease of unknown etiology which currently affects approximately 7.5 % of the adult population ( ). Asthma is an inflammatory disorder of the airways. Airwa...
This study involves a FDA approved drug, Omalizumab, used in the treatment of moderate to severe allergic asthma that cannot be controlled by standard treatment. It works on IgE to contro...
This was a multicenter, randomized, double-blind, parallel-group, three-arm, placebo-controlled study designed to demonstrate the efficacy of two different formulations of omalizumab compa...
The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidan...
Asthma and allergic rhinitis are two of the most widespread chronic medical conditions. Asthma, a condition which encompasses chronic inflammation of the lower airway resulting in expiratory obstructi...
In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disea...
This review has discussed a link between allergic rhinitis, asthma and systemic lupus erythematosus (SLE) and a case report in this area. A clear link with symptoms of allergic rhinitis, asthma and SL...
Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthm...
A natural tocopherol with less antioxidant activity than alpha-tocopherol. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. As in GAMMA-TOCOPHEROL, it also has three methyl groups on the 6-chromanol nucleus but at different sites.
A natural tocopherol with less antioxidant activity than ALPHA-TOCOPHEROL. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. As in BETA-TOCOPHEROL, it also has three methyl groups on the 6-chromanol nucleus but at different sites.
A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.
A long-acting, non-sedative antihistaminic used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria. The drug is well tolerated and has no anticholinergic side effects.
Hypersensitivity reaction (ALLERGIC REACTION) to fungus ASPERGILLUS in an individual with long-standing BRONCHIAL ASTHMA. It is characterized by pulmonary infiltrates, EOSINOPHILIA, elevated serum IMMUNOGLOBULIN E, and skin reactivity to Aspergillus antigen.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Asthma is caused by inflammation of small tubes, called bronchi, which carry air in and out of the lungs. If you have asthma, the bronchi will be inflamed and more sensitive than normal. When you come into contact with something that irritates your...
Asthma COPD Cystic Fibrosis Pneumonia Pulmonary Medicine Respiratory Respiratory tract infections (RTIs) are any infection of the sinuses, throat, airways or lungs. They're usually caused by viruses, but they can also ...