Presented at the Triological Society Southern Section Meeting, Orlando, Florida, U.S.A., February 4–7, 2010.
Article first published online: 20 APR 2010
Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 120, Issue 5, pages 1051–1056, May 2010
How to Cite
Virgin, F., Zhang, S., Schuster, D., Azbell, C., Fortenberry, J., Sorscher, E. J. and Woodworth, B. A. (2010), The bioflavonoid compound, sinupret, stimulates transepithelial chloride transport in vitro and in vivo. The Laryngoscope, 120: 1051–1056. doi: 10.1002/lary.20871
This research was funded by the American Rhinologic Society New Investigator Award (2009) and Flight Attendant's Medical Research Institute Young Clinical Scientist Award (072218) to Bradford A. Woodworth.
Dr. Sorscher serves as a consultant for a Birmingham start up company (PNP Therapeutics, Inc.) but is not employed by the company and draws no salary from the company. His consulting includes a role as Director/Officer. He acts as a consultant with the approval of UAB and the UAB CIRB. He is compensated for consulting with stock. This company has no relationship to the current article. Dr. Sorscher and Dr. Woodworth are inventors on a patent submitted regarding the possible activity of chloride secretagogues for therapy of sinus disease (Provisional Patent Application Under 35 U.S.C. §111(b) and 37 C.F.R. §1.53(c) in the United States Patent and Trademark Office). Dr. Woodworth is a consultant for Gyrus ENT, ArthroCare ENT, and is on the GlaxcoSmithKline speaker's bureau.
- Issue published online: 21 APR 2010
- Article first published online: 20 APR 2010
- Manuscript Accepted: 7 JAN 2010
- Transepithelial ion transport;
- cystic fibrosis transmembrane conductance regulator;
- chronic sinusitis;
- chloride secretion;
- murine nasal culture;
- mucociliary clearance;
- nasal potential difference;
- Level of Evidence: 1a.
Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance in sinonasal epithelium leading to chronic rhinosinusitis. Abnormal chloride (Cl−) transport is one mechanism that contributes to this disorder, as demonstrated by the disease cystic fibrosis. Identifying safe compounds that stimulate transepithelial Cl− transport is critical to improving hydration of the ASL and promoting mucociliary transport. Sinupret (Bionorica, LLC, San Clemente, CA), a combination of naturally occurring bioflavonoids, is a widely used treatment for respiratory ailments in Europe. However, the effects of Sinupret on target respiratory epithelium have yet to be fully investigated. The present study evaluated the mechanisms underlying this bioflavonoid therapeutic on transepithelial Cl− transport in respiratory epithelium.
In vitro and in vivo investigation.
Well characterized murine nasal septal epithelial (MNSE) cultures, and murine nasal potential difference (NPD) techniques were used to evaluate the effects of Sinupret on Cl− secretion.
The change in Sinupret-stimulated current (Δ ISC expressed as μA/cm2) in MNSE, representing Cl− secretion, was significantly increased when compared to controls (19.04 ± 1.67 μA/cm2 vs. 1.8 ± 0.35 μA/cm2, respectively; P = .00005). Transepithelial Cl− transport measured in the murine NPD in vivo assay (n = 42) was also significantly enhanced when compared to controls (−0.8 mV vs. −0.9 mV; P = .0004). Importantly, Sinupret-stimulated Cl− transport was substantially more robust in vivo than forskolin, a compound among the strongest known cystic fibrosis transmembrane conductance regulator activators (−3.8 mV vs. −1.65 mV; P = .01).
Sinupret strongly activates transepithelial Cl− secretion through a mechanism known to hydrate the ASL of respiratory epithelium. This is one means by which the medication is likely to exert therapeutic benefit. Laryngoscope, 2010