BACKGROUND: Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-α-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. METHODS: Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F(2)-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. RESULTS: Following supplementation of natural-source d-α-tocopheryl acetate, plasma concentrations of α-tocopherol increased and γ-tocopherol decreased. Both baseline and allergen-induced F(2)-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-α-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-α-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. CONCLUSIONS: Inhibition of oxidant stress by natural-source d-α-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial.
BACKGROUND:Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-α-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. METHODS: Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F(2)-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. RESULTS: Following supplementation of natural-source d-α-tocopheryl acetate, plasma concentrations of α-tocopherol increased and γ-tocopherol decreased. Both baseline and allergen-induced F(2)-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-α-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-α-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. CONCLUSIONS: Inhibition of oxidant stress by natural-source d-α-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial.
Authors: Prescott G Woodruff; Barmak Modrek; David F Choy; Guiquan Jia; Alexander R Abbas; Almut Ellwanger; Laura L Koth; Joseph R Arron; John V Fahy Journal: Am J Respir Crit Care Med Date: 2009-05-29 Impact factor: 21.405
Authors: Johan D Boot; Sanne de Haas; Svetlana Tarasevych; Christine Roy; Lin Wang; Dilip Amin; Judith Cohen; Peter J Sterk; Barry Miller; Anne Paccaly; Jacobus Burggraaf; Adam F Cohen; Zuzana Diamant Journal: Am J Respir Crit Care Med Date: 2006-12-14 Impact factor: 21.405
Authors: Christopher G Slatore; Alyson J Littman; David H Au; Jessie A Satia; Emily White Journal: Am J Respir Crit Care Med Date: 2007-11-07 Impact factor: 21.405
Authors: J C Virchow; C Walker; D Hafner; C Kortsik; P Werner; H Matthys; C Kroegel Journal: Am J Respir Crit Care Med Date: 1995-04 Impact factor: 21.405
Authors: Emma K Larkin; Yu-Tang Gao; Tebeb Gebretsadik; Terryl J Hartman; Pingsheng Wu; Wanqing Wen; Gong Yang; Chunxue Bai; Meiling Jin; L Jackson Roberts; Myron Gross; Xiao O Shu; Tina V Hartert Journal: Am J Respir Crit Care Med Date: 2015-01-01 Impact factor: 21.405
Authors: V V Polosukhin; I V Polosukhin; A Hoskins; W Han; R Abdolrasulnia; T S Blackwell; R Dworski Journal: Allergy Date: 2014-10-01 Impact factor: 13.146
Authors: Yueh-Ying Han; Josh Blatter; John M Brehm; Erick Forno; Augusto A Litonjua; Juan C Celedón Journal: Lancet Respir Med Date: 2013-07-31 Impact factor: 30.700
Authors: Aimee Hoskins; Sara Reiss; Pingsheng Wu; Ning Chen; Wei Han; Rui-hong Do; Rasul Abdolrasulnia; Ryszard Dworski Journal: Am J Respir Crit Care Med Date: 2012-11-29 Impact factor: 21.405
Authors: Diana C Contreras Healey; Jacqueline Y Cephus; Sierra M Barone; Nowrin U Chowdhury; Debolanle O Dahunsi; Matthew Z Madden; Xiang Ye; Xuemei Yu; Kellen Olszewski; Kirsten Young; Valerie A Gerriets; Peter J Siska; Ryszard Dworski; Jonathan Hemler; Jason W Locasale; Masha V Poyurovsky; R Stokes Peebles; Jonathan M Irish; Dawn C Newcomb; Jeffrey C Rathmell Journal: J Immunol Date: 2021-02-08 Impact factor: 5.422