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The bioflavonoid compound, sinupret, stimulates transepithelial chloride transport in vitro and in vivo
Author(s) -
Virgin Frank,
Zhang Shaoyan,
Schuster Daniel,
Azbell Christopher,
Fortenberry James,
Sorscher Eric J.,
Woodworth Bradford A.
Publication year - 2010
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.20871
Subject(s) - transepithelial potential difference , in vivo , cystic fibrosis transmembrane conductance regulator , respiratory epithelium , chemistry , mucociliary clearance , respiratory system , cystic fibrosis , epithelium , forskolin , pharmacology , in vitro , ion transporter , medicine , pathology , biochemistry , biology , lung , membrane , microbiology and biotechnology
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 I SC expressed as μA/cm 2 ) in MNSE, representing Cl − secretion, was significantly increased when compared to controls (19.04 ± 1.67 μA/cm 2 vs. 1.8 ± 0.35 μA/cm 2 , 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