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Suppressive effects of nitric oxide‐releasing prednisolone NCX‐1015 on the allergic pleural eosinophil recruitment in rats
Author(s) -
Oliveira M. S. S.,
De O. Barreto E.,
Zamuner S.,
Pires A. L. A.,
Ferreira T. P. T.,
Cordeiro R. S. B.,
Lagente V.,
Martins M. A.,
Wallace J. L.,
E Silva P. M. R.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.03083.x
Subject(s) - prednisolone , eosinophil , eotaxin , pharmacology , chemistry , inflammation , nitric oxide , endocrinology , medicine , immunology , asthma
Summary Background The addition of a nitric oxide (NO)‐releasing moiety to prednisolone was shown to enhance the anti‐inflammatory activity of this glucocorticoid in some experimental conditions, but its effectiveness in the context of eosinophilic inflammation remains to be elucidated. Objective This study compared the anti‐inflammatory effect of prednisolone to a NO‐releasing derivative of prednisolone, NCX‐1015, using a model of allergen‐evoked eosinophil recruitment in rats. The efficacy of a NO‐donor compound, DETA‐NONOate, was also assessed for comparison. Methods Wistar rats were actively sensitized with Al(OH) 3 plus ovalbumin and 14 days later challenged with antigen intrapleurally. Treatments were performed locally 1 h before challenge. Cysteinyl‐leucotrienes (Cys‐LT) and eotaxin were measured by ELISA. Results Antigen challenge induced an eosinophil infiltration at 12 h, maximal at 24 h. It also caused an increase in the levels of Cys‐LTs in the pleural exudate and in the expression of 5‐lipoxygenase (5‐LO) in infiltrated leucocytes at 6 h, peaking at 12 h and persisting for at least 24 h. Treatment with equimolar doses of prednisolone and NCX‐1015 inhibited the late eosinophil infiltration, although the dose required to produce maximal inhibition was about one‐tenth that of prednisolone. Cys‐LT generation and 5‐LO expression were inhibited by NCX‐1015 but not by prednisolone. Treatment with prednisolone combined with the NO‐donor DETA‐NONOate led to a greater inhibition of the eosinophilia and Cys‐LT generation as compared with either drug alone. Administration of the steroid receptor antagonist RU 486, 1 h before prednisolone and NCX‐1015, abolished the inhibitory effect of the former, under conditions where it only partially affected the latter. Conclusions Our findings indicate that NCX‐1015 provided a greater anti‐inflammatory effect than prednisolone on the allergic eosinophil recruitment in rats, suggesting that NO‐releasing steroids can be considered as a promising therapeutic approach to allergic diseases.