title: Fenretinide prevents inflammation and airway hyperresponsiveness in a mouse model of allergic asthma.
abstract: Arachidonic acid (AA) and docosahexaenoic acid (DHA) play important roles in inflammation and disease progression, where AA is viewed as proinflammatory and DHA as antiinflammatory. We observe in our model of allergic asthma that the AA/DHA ratio is significantly skewed in a proinflammatory direction. Fenretinide, a vitamin A derivative, has been shown to correct fatty acid imbalances in other diseases. Therefore, we explored if fenretinide can have a protective effect in allergic asthma. To accomplish this, we measured the levels of AA and DHA in the lungs of nonallergic, ovalbumin-induced allergic, and fenretinide-treated allergic mice. We also investigated the effect of allergic asthma and fenretinide treatment on markers of oxidative stress, levels of metabolites, IgE production, airway hyperresponsiveness, and histological changes. Our data demonstrate that treatment of allergen-sensitized mice with fenretinide before allergen challenge prevents ovalbumin-induced changes in the AA/DHA ratio. The levels of several metabolites, such as serotonin, and markers of cellular stress, which are increased after ovalbumin challenge, are also controlled by fenretinide treatment. We observed the protective effect of fenretinide against ovalbumin-induced airway hyperresponsiveness and inflammation in the lungs, illustrated by a complete block in the infiltration of inflammatory cells to the airways and dramatically diminished goblet cell proliferation, even though IgE remained high. Our results demonstrate that fenretinide is an effective agent targeting inflammation, oxidation, and lung pathology observed in allergic asthma.
authors.affiliation: 1 Department of Human Genetics, and.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kanagaratham
authors.forename: Alžběta
authors.initials: A
authors.lastname: Kalivodová
authors.forename: Lukáš
authors.initials: L
authors.lastname: Najdekr
authors.forename: David
authors.initials: D
authors.lastname: Friedecký
authors.forename: Tomáš
authors.initials: T
authors.lastname: Adam
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.forename: Juan Bautista
authors.initials: JB
authors.lastname: De Sanctis
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D017313:Fenretinide / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D017313:Fenretinide; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: allergic asthma; arachidonic acid; docosahexaenoic acid; fenretinide; inflammation