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Keywords:

  • Transepithelial ion transport;
  • Sinupret;
  • cystic fibrosis transmembrane conductance regulator;
  • chronic sinusitis;
  • chloride secretion;
  • murine nasal culture;
  • mucociliary clearance;
  • nasal potential difference;
  • Level of Evidence: 1a.

Abstract

Objectives/Hypothesis:

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.

Study Design:

In vitro and in vivo investigation.

Methods:

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.

Results:

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).

Conclusions:

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