Effect of in vitro and in vivo aerosolized treatment with geniposide on tracheal permeability in ovalbumin-induced guinea pigs.
The primary objective of this study was to investigate the effect of geniposide, a potent anti-inflammatory, on ovalbumin-antigen-induced tracheal permeability and transepithelial electrical resistance in guinea pigs. Two weeks after sensitization with ovalbumin (100 mg/ml), the permeability of guinea-pig tracheas was evaluated by flux measurements using the transcellular tracer, [(14)C]estradiol, and the paracellular tracer, [(14)C]mannitol. The effect of extracellular Ca(2+) with geniposide was also studied, using deletion of Ca(2+) in the donor chamber. The in vivo treatment effect of aerosolized geniposide on tracheal permeability in the ovalbumin-sensitized guinea pigs was also evaluated. The results indicate that tight junction permeability of ovalbumin-sensitized trachea was significantly dose dependent and decreased by geniposide (1-10 mM), as evidenced by substantial recovery of transepithelial electrical resistance and decreased transepithelial permeability of [(14)C]mannitol at (1.32+/-0.12) x 10(-5) cm/s. The effect of combination of the removal of extracellular Ca(2+) with geniposide had no effect on tight junction permeability of ovalbumin-sensitized trachea and revealed that transepithelial electrical resistance and junction permeability did not recover. In addition, the cAMP levels and phosphodiesterase activity were not significantly influenced in ovalbumin-sensitized tracheal tissues after geniposide treatment. Inhaled geniposide (50 mM, 30 min after ovalbumin sensitization) significantly restored junction permeability induced by ovalbumin (100 mg/ml, 2 min). Junction permeability did not recover on pretreatment with geniposide (50 mM for 30 min over 16 days consecutive before ovalbumin sensitization) after exposure of conscious guinea pigs to aerosol ovalbumin. In conclusion, geniposide has inhibitory effects on ovalbumin-induced junction permeability and recovery of transepithelial electrical resistance in guinea pig trachea, showing its potential as anti-asthma therapy.
Liaw
J
J
Department of Pharmaceutics, School of Pharmacy, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan. jhorng@tmu.edu.tw
Chao
Y C
YC
D000336:Aerosols; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000600:supply & distribution*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D039823:Iridoids; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D010047:Ovalbumin / Q000276:immunology; D010539:Permeability; D011714:Pyrans / Q000008:administration & dosage*; D019108:Tight Junctions / Q000187:drug effects; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D039823:Iridoids; D011714:Pyrans; C007835:geniposide; D008353:Mannitol; D010047:Ovalbumin; D000242:Cyclic AMP; D002118:Calcium