Lack of effect of oral sulforaphane administration on Nrf2 expression in COPD: A randomized, double-blind, placebo controlled trial

Robert A Wise, Janet Teresa Holbrook, Gerard Criner, Sanjay Sethi, Sobharani Rayapudi, Kuladeep R. Sudini, Elizabeth Sugar, Alyce Burke, Rajesh Thimmulappa, Anju Singh, Paul Talalay, Jed W Fahey, Charles S. Berenson, Michael R. Jacobs, Shyam Biswal, Gwen Leatherman, Marie Daniel, April Thurman, Nathaniel Marchetti, Victor KimKartik Shenoy, Heidi Smith, Maria Rosario, Sudheer Bolla, Chenna Mandapati, Ellana Eberhardt, Ragina Kruzel, Sarvesh Kumar, Sanjeev Noel, Aleksandra Beselman, Debra Amend-Libercci, Cathy Ewing, Adante Hart, Andrea Lears, Deborah Nowakowski, Nancy Prusakowski, Dave Shade, Razan Yasin, Ellen Brown, Lucy Wang, George O'Connor, Charlie Strange, Christine Wendt, Anthony Punturieri, Lisa Weber Viviano

Research output: Contribution to journalArticle

Abstract

Background: 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). Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article numbere0163716
JournalPLoS One
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Wise, R. A., Holbrook, J. T., Criner, G., Sethi, S., Rayapudi, S., Sudini, K. R., Sugar, E., Burke, A., Thimmulappa, R., Singh, A., Talalay, P., Fahey, J. W., Berenson, C. S., Jacobs, M. R., Biswal, S., Leatherman, G., Daniel, M., Thurman, A., Marchetti, N., ... Viviano, L. W. (2016). Lack of effect of oral sulforaphane administration on Nrf2 expression in COPD: A randomized, double-blind, placebo controlled trial. PLoS One, 11(11), [e0163716]. https://doi.org/10.1371/journal.pone.0163716