title: Effects of alpha tocopherol and probucol supplements on allergen-induced airway inflammation and hyperresponsiveness in a mouse model of allergic asthma.
abstract: OBJECTIVE
  We investigated the role of antioxidants in airway hyperresponsiveness to acetylcholine using young asthma model mice, which were sensitized and stimulated with ovalbumin.
  
  
  METHODS
  The mice had been fed either a normal diet, an alpha-tocopherol-supplemented diet or a probucol-supplemented diet 14 days before the first sensitization. They were immunized with antigen at intervals of 12 days and, starting from 10 days after the second immunization, they were exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty-four hours after the last antigen inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected. A blood and lung tissue study was also carried out.
  
  
  RESULTS
  Twenty-four hours after the last antigen challenge, both IL-4 and IL-5 in the BALF of alpha-tocopherol-supplemented mice were significantly decreased. The IL-5 level in probucol-supplemented mice was also decreased, but there was no difference in IL-4 levels. The serum IgE level was decreased in probucol-supplemented mice. Differential cell rates of the fluid revealed a significant decrease in eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to acetylcholine was also repressed in antioxidant-supplemented mice. In histological sections of lung tissue, inflammatory cells and mucus secretion were markedly reduced in antioxidant-supplemented mice. We investigated the antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung tissue, and acrolein in BALF; however, our experiment gave us no evidence of the antioxidant properties of either alpha-tocopherol or probucol contributing to the reduction of airway inflammation.
  
  
  CONCLUSIONS
  These findings indicate that alpha-tocopherol and probucol suppress allergic responses in asthma model mice, although these two drugs cause suppression in different ways that are unrelated to antioxidation.
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki City, Osaka Prefecture, Japan. ped029@poh.osaka-med.ac.jp
authors.forename: Nami
authors.initials: N
authors.lastname: Okamoto
authors.forename: Takuji
authors.initials: T
authors.lastname: Murata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000171:Acrolein / Q000032:analysis; D000485:Allergens / Q000276:immunology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000150:complications / Q000188:drug therapy; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D011341:Probucol / Q000097:blood / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000485:Allergens; D000975:Antioxidants; D015848:Interleukin-5; D015847:Interleukin-4; C075750:8-epi-prostaglandin F2alpha; D007073:Immunoglobulin E; D000171:Acrolein; D010047:Ovalbumin; D015237:Dinoprost; D024502:alpha-Tocopherol; D011341:Probucol