ISSN:
1432-1041
Keywords:
Azelastine
;
Polymorphonuclear leukocytes
;
Respiratory burst oxidase
;
alveolar macrophage
;
superoxide
;
superoxide dismutase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O 2 - ) generation by human PMN in a dose-and time-dependent manner. Phorbol myristyl acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O 2 - generation were strongly suppressed by 10−6M and 10−5M Azeptin, respectively. PMN and PAM from rabbits injected with Azeptin 0.2 mg·kg−1 for 5 days showed lower chemiluminescence and O 2 - generation than cells from untreated rabbits. Nitroblue tetrazolium reduction activity in human PMN was suppressed by treatment of PMN with 10−6M Azeptin for 6 h. Inositol trisphosphate, intracellular free calcium, and protein kinase C activity were decreased by 10−6M to 10−5M Azeptin. The tyrosine phosphorylation of many proteins, especially a 115 kDa protein, was suppressed by 10−5M Azeptin. However, superoxide dismutase activity in PMN, PAM, and lung tissue samples was only slightly decreased, even when the rabbits were treated with 1.0 mg·kg−1 Azeptin for 5 days. The results suggest that Azeptin suppresses multiple signal transduction steps in the respiratory burst of PMN. This suppressive action should be very useful in the prevention and treatment of reactive oxygen-associated disorders.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00194963
