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Prostaglandins Other Lipid Mediat ; 95(1-4): 27-34, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21601002

RESUMO

Although it has been suggested that prostaglandin (PG) D(2) is involved in the pathogenesis of allergic rhinitis, whether the inhibition of hematopoietic PGD(2) synthase (H-PGDS) shows beneficial effects on allergic rhinitis has been unclear. We evaluated the effects of a selective H-PGDS inhibitor, TFC-007, on nasal symptoms on Japanese cedar pollen-induced allergic rhinitis of guinea pigs. Sensitized animals were challenged with the pollen once a week. TFC-007 (30mg/kg, p.o.) given once before a challenge almost completely suppressed PGD(2) production in the nasal tissue early and late after the challenge. Although pre-treatment did not affect the incidences of sneezing and early phase nasal blockage, late phase nasal blockage was partially but significantly attenuated; however, nasal eosinophilia was not suppressed. In contrast, when TFC-007 was given once 1.5h after the challenge, the late phase response was not affected. Collectively, PGD(2) produced by H-PGDS early after an antigen challenge can participate in the induction of late phase nasal blockage, although the mechanism may be independent of eosinophil infilatration. The strategy for H-PGDS inhibition may be beneficial for allergic rhinitis therapy.


Assuntos
Eosinofilia/prevenção & controle , Oxirredutases Intramoleculares/antagonistas & inibidores , Lipocalinas/antagonistas & inibidores , Obstrução Nasal/prevenção & controle , Rinite Alérgica Sazonal/prevenção & controle , Alérgenos/efeitos adversos , Animais , Cryptomeria , Ensaios Enzimáticos , Eosinofilia/etiologia , Eosinófilos/patologia , Cobaias , Humanos , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/metabolismo , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Líquido da Lavagem Nasal/citologia , Obstrução Nasal/etiologia , Pólen/efeitos adversos , Prostaglandina D2/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Rinite Alérgica Sazonal/etiologia , Espirro/efeitos dos fármacos
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