15 research outputs found
Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.
COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels.Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.Clinicaltrials.gov: NCT01335971
Correction: Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.
[This corrects the article DOI: 10.1371/journal.pone.0163716.]
Correction: Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial
Relative changes in gene expression by treatment group in bronchial epithelial cells.
<p>Treatments are labeled as placebo (no sulforaphane), 25 μM) and 150 μM of sulforaphane. Gene identifiers are listed along the x-axis. The y-axis displays the distribution of fold-change in gene expression (follow-up divided by baseline).</p
Baseline characteristics of randomized participants by treatment group.
<p>Baseline characteristics of randomized participants by treatment group.</p
Fold-change<sup>*</sup> in genetic expression in bronchial epithelial cells and alveolar macrophages by treatment group.
<p>Fold-change<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163716#t003fn001" target="_blank">*</a></sup> in genetic expression in bronchial epithelial cells and alveolar macrophages by treatment group.</p
Baseline measures of antioxidants and markers of inflammation by treatment group.
<p>Baseline measures of antioxidants and markers of inflammation by treatment group.</p
Fold-change<sup>*</sup> in inflammatory marker concentrations by treatment group.
<p>Fold-change<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163716#t004fn002" target="_blank">*</a></sup> in inflammatory marker concentrations by treatment group.</p
Dithiocarbamate (DTC) concentration in 21 randomly selected plasma samples.
<p>Treatments are labeled as placebo (no sulforaphane), 25 μM, and 150 μM of sulforaphane.</p