Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.
Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level. Inhibition of free oxygen radical generation in isolated neutrophils by dithiaden resulted from the inhibition of protein kinase C activation. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden and suggestive of increasing the apoptosis of professional phagocytes. Of the H₃/H₄antihistamines, the most effective was JNJ7777120 in decreasing chemiluminescence in whole blood and also at extra- and intracellular sites of isolated neutrophils. JNJ 10191584 and thioperamide were less effective and the latter significantly potentiated free oxygen radical generation intracellularly. The results demonstrated that, compared with the H₃/H₄antihistamines investigated, H₁antihistamines were much more potent in inhibiting free oxygen radical generation in human professional phagocytes. This finding should be taken into account therapeutically.
Department of Cellular Pharmacology, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic. radomir.nosal@savba.sk.
Radomír
R
Nosáľ
Viera
V
Jančinová
Katarína
K
Drábiková
Tomáš
T
Perečko
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006633:Histamine Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010586:Phagocytes / Q000187:drug effects / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology*
D006633:Histamine Antagonists