[Influences of anti-allergic drugs on superoxide generation from the hypoxanthine-xanthine oxidase system or polymorphonuclear leukocytes].
The influences of anti-allergic drugs on superoxide generation from the hypoxanthine-xanthine oxidase system or polymorphonuclear leukocytes (PMN) were studied by an electron spin resonance assay using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapper. The intensity of DMPO-OOH signal generated from the hypoxanthine-xanthine oxidase system was not influenced by the presence of azelastine, ketotifen, disodium cromoglycate, mequitazine, or methylprednisolone, but it decreased in the presence of AA-673. A kinetic study showed that the second order rate constant for reaction between AA-673 and superoxide anion at pH 7.4 was 2.9 x 10(8)M-1S-1. The relative intensity of DMPO-OOH spin adduct generated from PMN stimulated with phorbol myristate acetate (PMA) or opsonized zymosan (OZ) significantly decreased in the presence of azelastine: from the PMN-PMA system, with 10.7 microM concentration of molar concentration causing 50% reduction of the signal intensity (IC50), while from the PMN-OZ system, with 10.5 microM concentration of IC50, and also decreased in the presence of mequitazine: from the PMN-PMA system, with 10.8 microM concentration of IC50, while from the PMN-OZ system, less than 2.0 microM concentration of IC50. These results suggest that some anti-allergic drugs may have anti-inflammatory and anti-oxidative actions due to scavenging superoxide radicals or due to inhibiting superoxide production.
Yoshikawa
T
T
Naito
Y
Y
Takahashi
S
S
Tanigawa
T
T
Oyamada
H
H
Ueda
S
S
Takemura
T
T
Sugino
S
S
Kondo
M
M
D000631:Aminopyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D010640:Phenothiazines / Q000494:pharmacology*; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D013482:Superoxide Dismutase; D013481:Superoxides / Q000037:antagonists & inhibitors*
D000631:Aminopyridines; D005609:Free Radicals; D006634:Histamine H1 Antagonists; D010640:Phenothiazines; D010793:Phthalazines; D011724:Pyridazines; D013481:Superoxides; C045742:amlexanox; D013482:Superoxide Dismutase; C006069:mequitazine; C020976:azelastine