Details

Autor(en) / Beteiligte

• Neves, Josiane S.
• Lima, Lídia M.
• Fraga, Carlos A.M.
• Barreiro, Eliezer J.
• Miranda, Ana L.P.
• Diaz, Bruno L.
• Balduino, Alex
• Siqueira, Rodrigo de Azeredo
• e Silva, Patrícia M.R.
• Martins, Marco A.

Titel

Evaluating the prophylactic potential of the phtalimide derivative LASSBio 552 on allergen-evoked inflammation in rats

Ist Teil von

• European journal of pharmacology, 2005-03, Vol.511 (2), p.219-227

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2005

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• A previous study showed that the novel tetrazolephtalimide derivative LASSBio 552 (2-4-[3-(1 H-1,2,3,4-tetraazol-5-yl)propoxy]phenethyl-1,3-isoindolinedione) prevents LTD 4-evoked tracheal contraction. This led us to examine the putative anti-inflammatory effect of LASSBio 552 in comparison with the leukotriene CysLT 1 receptor antagonist zafirlukast using a model of allergic pleurisy in rats. Treatment with either LASSBio 552 (24–96 μmol/kg, i.p.) or zafirlukast (9–72 μmol/kg, i.p.), 1 h before challenge, inhibited eosinophil and mononuclear cell influx into the pleural cavity 24 h post-challenge, but failed to alter the increased levels of eotaxin, plasma leakage, mast cell degranulation and neutrophil infiltration noted 6 h post-challenge. CD4 + T cell recruitment 24 h post-challenge was also sensitive to LASSBio 552. This treatment failed to alter cysteinyl leukotriene production at 6 h, but clearly inhibited the phenomenon 24 h and 48 h post-challenge. In in vitro settings LASSBio 552 inhibited allergen-evoked cysteinyl leukotriene generation from isolated mast cells, while histamine release remained unchanged. It also slightly inhibited cysteinyl leukotriene production by eosinophils and mononuclear cells triggered by Ca +2 ionophore A23187. A leukotriene CysLT 1 receptor transfected cell-based assay revealed that LASSBio 552 did not prevent LTD 4-evoked Ca +2 influx, indicating that it was not a leukotriene CysLT 1 receptor antagonist. These findings indicate that LASSBio 552 is able to inhibit eosinophil influx triggered by allergen chalenge in a mechanism at least partially associated with suppression of CD4 + T cell influx and cysteinyl leukotriene production.