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Intranasal administration of a combination of choline chloride,vitamin C,and selenium attenuates the allergic effect in a mouse model of airway disease
Institution:1. Allergy and Immunology Section, Council of Scientific and Industrial Research–Institute of Genomics and Integrative Biology, Delhi 110007, India;2. Department of Biotechnology, University of Pune, Ganeshkhind, Pune 411 007, India;1. Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovak Republic;2. Department of Glycomaterials, Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 842 38 Bratislava, Slovak Republic;1. Department of Pharmacognosy, VNS Institute of Pharmacy, Bhopal (M.P.) 462044, India;2. Department of Pharmaceutical Sciences, Dr. H.S. Gour Central University, Sagar (M.P.) 470003, India;1. MRC and Asthma-UK Centre for Allergic Mechanisms in Asthma, King''s College London, London, United Kingdom;2. Centre for Primary Care and Public Health, Blizard Institute, Queen Mary, University of London, London, United Kingdom;3. Homerton University NHS Foundation Trust, London, United Kingdom;1. Department of Respiratory Diseases, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing 210029, China;2. The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, China;3. Department of Molecular Biology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing 210029, China;1. Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia;2. School of Medicine, University of Queensland, Queensland, Australia;1. Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA;2. Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA;3. Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA;4. Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA;5. Department of Neurology and Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA
Abstract:Respiratory allergic disease is an inflammatory condition accompanied by oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants may have a therapeutic effect. In this study, the effects of choline chloride in combination with antioxidants were evaluated via the intranasal route in a mouse model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and 14 and challenged on days 25–30 with cockroach extract (CE) and with a booster challenge on day 38. They were treated with choline chloride (ChCl; 1 mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1 mg/kg) alone or in combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs, and spleen. Mice immunized with CE showed a significant increase in airway hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative stress markers intracellular reactive oxygen species and 8-isoprostanes compared to the phosphate-buffered saline control group. A significant decrease was observed in these parameters with all the treatments (p<0.01). The highest decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to the normal level. This group also showed the highest decrease in airway inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF-κB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase activity, which was decreased significantly in CE-immunized mice, was restored to normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized mice and was restored to normal by combination treatment. The combination treatment induced FOXP3+ cells in splenocyte culture, responsible for the upregulation of IL-10. In conclusion, the combination of choline chloride, vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and oxidative stress, probably by causing IL-10 production by FOXP3+ cells, and possesses therapeutic potential against allergic airway disease.
Keywords:Antioxidants  Allergy  Airway inflammation  Immunoregulation  Reactive oxygen species  Oxidative stress  Therapy  Free radicals
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