Extra- and intracellular formation of reactive oxygen species by human neutrophils in the presence of pheniramine, chlorpheniramine and brompheniramine.
BACKGROUND
Allergic inflammation was found to be accompanied by activation of neutrophils. Since this resulted in increased formation of reactive oxygen species, the antioxidative activity of antiallergic drugs was considered to decrease the risk of tissue damage. However, if the drug-induced inhibition of radical formation occurred intracellularly, it could disturb regulation of neutrophil functions and decrease bactericidal activity of these cells. Separate analysis of extra- and intracellular activity of antioxidative drugs is thus of particular importance.


OBJECTIVE
To differentiate the effects of three antiallergic H1-antihistamine drugs (pheniramine, chlor- and brompheniramine) on radical formation outside and inside human neutrophils.


METHODS
Formation of reactive oxygen species was determined in vitro using the chemiluminescence method. The chemiluminescence signal, initiated by phorbol-12-myristate-13-acetate, was enhanced either with isoluminol (extracellular) or with luminol in the presence of extracellular scavengers, superoxide dismutase and catalase (intracellular).


RESULTS
The antihistamines tested displayed dual activity - they inhibited the extracellular and potentiated the intracellular chemiluminescence. Chlor- and brompheniramine were found to be more effective than pheniramine.


CONCLUSIONS
Compared to other H1-antihistamines (such as dithiaden or loratadine, active both extra- and intracellularly), the observed inhibition caused by the pheniramines tested was unique since it occurred selectively outside neutrophils. This might indicate the ability of these drugs to minimise toxic effects of extracellular radicals without affecting intracellular oxidant production involved in regulation of neutrophil functions and in microbial killing.
Jancinová
Viera
V
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. viera.jancinova@savba.sk
Drábiková
Katarína
K
Nosál'
Radomír
R
Holománová
Dagmar
D
D001977:Brompheniramine / Q000494:pharmacology*; D002744:Chlorpheniramine / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D049449:Luminescence; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010632:Pheniramine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D017382:Reactive Oxygen Species; D010632:Pheniramine; D002744:Chlorpheniramine; D001977:Brompheniramine