Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways

Robert Howard Brown, Curt Reynolds, Allison Brooker, Paul Talalay, Jed W Fahey

Research output: Contribution to journalArticle

Abstract

Background: It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients. Methods: Forty-five moderate asthmatics were administered sulforaphane (100μmol daily for 14days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption. Results: Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21%; p = 0.01) in 60% of these asthmatics. Interestingly, in 20% of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly. Conclusion: These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.

Original languageEnglish (US)
Article number106
JournalRespiratory Research
Volume16
Issue number1
DOIs
StatePublished - Sep 15 2015

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Methacholine Chloride
Bronchoconstrictor Agents
Genes
Phytochemicals
sulforafan
Anti-Inflammatory Agents
Antioxidants
Tomography
Lung
Airway Resistance
Brassica
Gene Expression
Therapeutics

Keywords

  • Asthma
  • Bronchodilation
  • Oxidative stress

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. / Brown, Robert Howard; Reynolds, Curt; Brooker, Allison; Talalay, Paul; Fahey, Jed W.

In: Respiratory Research, Vol. 16, No. 1, 106, 15.09.2015.

Research output: Contribution to journalArticle

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abstract = "Background: It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients. Methods: Forty-five moderate asthmatics were administered sulforaphane (100μmol daily for 14days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption. Results: Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21{\%}; p = 0.01) in 60{\%} of these asthmatics. Interestingly, in 20{\%} of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly. Conclusion: These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.",
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