On the pharmacology and toxicology of neutrophils.
OBJECTIVE
To study the effect of H1-antihistamines dithiaden (Dit) and loratadine (Lor) and compare it with that of histamine (His) on phorbolmyristate acetate (PMA) stimulated chemiluminescence (CL) of whole blood, isolated neutrophils, release of myeloperoxidase (MPO), and on superoxide (SO) generation.


METHODS
Luminol- and isoluminol-enhanced CL was applied for measuring the oxidative burst, spectrophotometry was used for determination of MPO (o-dianisidine) and SO generation (superoxide dismutase inhibition of cytochrome c).


RESULTS
Dit and Lor dose-dependently inhibited CL of whole blood and significantly decreased oxidative burst both at the extra- and intracellular sites of neutrophils. Release of MPO was decreased with both drugs tested in 10-times lower concentrations than was SO inhibition. Histamine (His) was much less effective in the inhibition of the parameters investigated.


CONCLUSIONS
Histaminergic drugs of the 1st generation inhibited oxidative burst of human phagocytes in whole blood and in isolated neutrophils. The rank order of potency to inhibit CL, MPO release and SO generation in PMA stimulated phagocytes was: Dit>Lor>His.
Nosál'
Radomir
R
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. exfarano@savba.sk
Drábiková
Katarína
K
Jancinová
Viera
V
Macicková
Tatiana
T
Pecivová
Jana
J
Holománová
Dagmar
D
D001582:Benzothiepins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D017336:Loratadine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001582:Benzothiepins; D006634:Histamine H1 Antagonists; C100170:dithiadene; D017336:Loratadine; D006632:Histamine; D009195:Peroxidase; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate