Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model.
We showed recently that IL-4 causes mitochondrial dysfunction in allergic asthma. IL-4 is also known to induce 12/15-lipoxygenase (12/15-LOX), a potent candidate molecule in asthma. Because vitamin E (Vit-E) reduces IL-4 and inhibits 12/15-LOX in vitro, here we tested the hypothesis that Vit-E may be effective in restoring key mitochondrial dysfunctions, thus alleviating asthma features in an experimental allergic murine model. Ovalbumin (OVA)-sensitized and challenged male BALB/c mice showed the characteristic features of asthma such as airway hyperresponsiveness (AHR), airway inflammation, and airway remodeling. In addition, these mice showed increase in the expression and metabolites of 12/15-LOX, reduction in the activity and expression of the third subunit of mitochondrial cytochrome-c oxidase, and increased cytochrome c in lung cytosol, which indicate that OVA sensitization and challenge causes mitochondrial dysfunction. Vit-E was administered orally to these mice, and 12/15-LOX expression, key mitochondrial functions, ultrastructural changes of mitochondria in bronchial epithelia, and asthmatic parameters were determined. Vit-E treatment reduced AHR, Th2 response including IL-4, IL-5, IL-13, and OVA-specific IgE, eotaxin, transforming growth factor-beta1, airway inflammation, expression and metabolites of 12/15-LOX in lung cytosol, lipid peroxidation, and nitric oxide metabolites in the lung, restored the activity and expression of the third subunit of cytochrome-c oxidase in lung mitochondria and bronchial epithelia, respectively, reduced the appearance of cytochrome c in lung cytosol, and also restored mitochondrial ultrastructural changes of bronchial epithelia. In summary, these findings show that Vit-E reduces key mitochondrial dysfunctions and alleviates asthmatic features.
Mabalirajan
Ulaganathan
U
Molecular Immunogenetics Laboratory, Inst. of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
Aich
Jyotirmoi
J
Leishangthem
Geeta Devi
GD
Sharma
Surendra Kumar
SK
Dinda
Amit Kumar
AK
Ghosh
Balaram
B
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010047:Ovalbumin; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
C475064:12-15-lipoxygenase; D018927:Anti-Asthmatic Agents; D018793:Interleukin-13; D015848:Interleukin-5; D008041:Linoleic Acids; D053773:Transforming Growth Factor beta1; D014810:Vitamin E; D015847:Interleukin-4; D007073:Immunoglobulin E; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D010047:Ovalbumin; D045304:Cytochromes c; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D003576:Electron Transport Complex IV