title: Intranasal administration of a combination of choline chloride, vitamin C, and selenium attenuates the allergic effect in a mouse model of airway disease.
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; 1mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/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.
authors.affiliation: Allergy and Immunology Section, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi 110007, India; Department of Biotechnology, University of Pune, Ganeshkhind, Pune 411 007, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Bansal
authors.affiliation: Allergy and Immunology Section, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi 110007, India; Department of Biotechnology, University of Pune, Ganeshkhind, Pune 411 007, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Saw
authors.affiliation: Allergy and Immunology Section, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Dhanapal
authors.initials: D
authors.lastname: Govindaraj
authors.affiliation: Allergy and Immunology Section, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi 110007, India. Electronic address: naveen@igib.res.in.
authors.forename: Naveen
authors.initials: N
authors.lastname: Arora
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002794:Choline / Q000494:pharmacology*; D003058:Cockroaches / Q000276:immunology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004338:Drug Combinations; D047209:Eosinophil Peroxidase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008082:Lipotropic Agents / Q000494:pharmacology; D008168:Lung / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D012643:Selenium / Q000494:pharmacology*; D013154:Spleen / Q000201:enzymology; D018418:Th2 Cells / Q000276:immunology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004338:Drug Combinations; C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D015848:Interleukin-5; D008082:Lipotropic Agents; D017382:Reactive Oxygen Species; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D016753:Interleukin-10; D015847:Interleukin-4; C075750:8-epi-prostaglandin F2alpha; D007073:Immunoglobulin E; D015237:Dinoprost; D047209:Eosinophil Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium; D002794:Choline; D001205:Ascorbic Acid
keywords: Airway inflammation; Allergy; Antioxidants; Free radicals; Immunoregulation; Oxidative stress; Reactive oxygen species; Therapy