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Clinical Trial
. 2015 Sep 15;16(1):106.
doi: 10.1186/s12931-015-0253-z.

Sulforaphane Improves the Bronchoprotective Response in Asthmatics Through Nrf2-mediated Gene Pathways

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Free PMC article
Clinical Trial

Sulforaphane Improves the Bronchoprotective Response in Asthmatics Through Nrf2-mediated Gene Pathways

Robert H Brown et al. Respir Res. .
Free PMC article

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 (100 μmol daily for 14 days), 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.

Figures

Fig. 1
Fig. 1
Time line of trial protocol
Fig. 2
Fig. 2
Negative correlation between the changes (%) resulting from sulforaphane (SF) administration on: a. bronchodilation (BD) and on b. bronchoprotection (BP) in asthmatic subjects, and the effects of sulforaphane administration on the reduction of FEV1 caused by MCh challenge. a: There was a significant negative correlation between the changes in BD and the changes in FEV1 (r2 = 0.13, p = 0.01). As the decrease in FEV1 with MCh challenge (airway narrowing) became larger with administration of sulforaphane, the BD response became smaller. b: There was a significant negative correlation between the changes in BP and the changes in FEV1 (r2 = 0.26, p = 0.0005). As the decrease in FEV1 with MCh challenge (airway narrowing) became larger with administration of sulforaphane, the BP response became smaller. The Mean control FEV1 was 2.7 ± 0.7 L, and a single MCh challenge caused a reduction in FEV1 by 0.78 ± 0.3 L. We further made the widely accepted assumption that the reproducibility of FEV1 values was 0.1 L, so that x-axis changes in Fig. 2a and b between −0.1 and +0.1 L were considered as no effect

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