Characterization of a model of tracheal plasma extravasation in passively sensitized rats using anti-allergic and anti-inflammatory drugs by oral and intratracheal route.
The aim of the following study was to characterize a passive systemic anaphylaxis rat model of dinitrophenyl (DNP)-induced plasma extravasation in the trachea to determine if the model is appropriate for the evaluation of new drugs targeting airway mast cells by oral and intratracheal (i.t.) route. To this purpose we have used fluticasone and a range of anti-allergic drugs including compounds either active on mast cell activation, such as cromoglycate and the Syk inhibitor R406, or active on mast cell mediators, such as cetirizine and montelukast. To further characterize the model, the effect of fluticasone, cromoglycate and R406 on rat tracheal mast cell degranulation was also assessed histologically. DNP-induced tracheal plasma extravasation was inhibited by cromoglycate (i.v. and i.t.) and R406 (p.o.), but not by fluticasone (i.t.), cetirizine or montelukast (p.o.). Cromoglycate and R406 also showed inhibition of tracheal mast cell degranulation, whereas fluticasone was inactive. These results suggest that the DNP-induced tracheal plasma extravasation model constitutes a useful animal model for the evaluation, by oral and i.t. route, of new anti-allergic drugs intended to target airway mast cells.
Respiratory Therapeutic Area - Discovery, Almirall, R&D Centre, Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain. cristina.carreno@almirall.com
Cristina
C
Carreño
Anna
A
Domènech
Neus
N
Prats
Montserrat
M
Miralpeix
Isabel
I
Ramis
D000085:Acetates / Q000494:pharmacology; D000284:Administration, Oral; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D017332:Cetirizine / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D003521:Cyclopropanes; D004140:Dinitrophenols / Q000494:pharmacology; D000068298:Fluticasone; D007116:Immunization, Passive; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D007442:Intubation, Intratracheal; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology; D010949:Plasma / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides; D000072377:Syk Kinase; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D000085:Acetates; D000730:Androstadienes; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D004140:Dinitrophenols; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; C510788:N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine; D010078:Oxazines; D011725:Pyridines; D011804:Quinolines; D013440:Sulfides; D000068298:Fluticasone; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; C093875:montelukast; D004205:Cromolyn Sodium; D017332:Cetirizine