Restoration of bronchoprotection and bronchodilation in asthma through stimulation

INTRODUCTION: Sulforaphane, a food compound found in cruciferous vegetables, specifically broccoli sprouts, potently induces a variety of cytoprotective enzymes (antioxidant and anti-inflammatory) via the Nrf2 signaling pathway, in a range of organ systems. Nrf2 is responsible for restoring cellular homeostasis through antioxidant mechanisms.

Disruption of the Nrf2 signaling pathway is a possible cause for chronic inflammation such as associated with asthma and could explain the recurrent exacerbations seen in patients with asthma. The absence of bronchoprotection (BP), the ability of deep inspirations to prevent subsequent spasmogen-induced airway constriction, is a major characteristic of even mild asthma. Bronchodilation (BD), the ability of deep inspirations to reverse prior spasmogen-induced airway constriction, is significantly depressed in asthmatics with severe airflow obstruction. We tested the hypothesis that consumption of Broccoli Sprout Extract (BSE) restores BP and BD in subjects with asthma.

METHODS: With IRB approval, 9 asthmatic subjects consumed BSE containing 100 micromoles of sulforaphane each evening for 14 days. We examined the effects of BSE on BD and BP as measured by FEV1 in subjects with and without airway obstruction (baseline FEV1/FVC less than 95% of predicted). We also measured exhaled nitric oxide (NO).

RESULTS: The baseline FEV1, FVC and FEV1/FVC (% predicted) were 89±4%, 99±6%, and 91±4% (mean±sem), respectively. Overall, BD increased from 29±9% at baseline to 38±10% after BSE, and BP increased from 19±15% at baseline to 30±15% after BSE. The change in BD and BP in the asthmatics with airway obstruction was more dramatic. In the obstructed asthmatics, BD increased from 10±11% at baseline to 34±8% after BSE, and BP increased from – 8±17% at baseline to 46±13% after BSE. NO increased in all but one of the asthmatics after BSE compared to baseline. NO at baseline was 14±4%, and increased to 20±5% after BSE. In the obstructed asthmatics, NO increased from 9±6% at baseline to 23±10% after BSE. There were no adverse events, and extensive clinical chemistries including liver and thyroid function tests revealed no abnormalities.

CONCLUSION: These data suggest that one potentially important factor that causes impairment of BP and BD in asthma, and leads to persistent obstructive disease, is dysfunction of the Nrf2-pathway. Furthermore, individuals with more chronic disease or ongoing exposure to oxidant stress, those with airway obstruction, derived greater benefit from activation of this antioxidant pathway.

Source: Am J Respir Crit Care Med 181;2010:A4986 /

[Poster Board # D1] Restoration of bronchoprotection and bronchodilation in asthma through stimulation of the Nrf2 pathway, [Publication Page: A4986] G. Pyrgos, MD, J. Fahey, ScD, P. Talalay, MD, C. Reynolds, MS, R. Brown, MD MPH Baltimore/US