Modulation of metabolic activity of phagocytes by antihistamines

Open access

Modulation of metabolic activity of phagocytes by antihistamines

The purpose of the study was to investigate the effects of H1-antihistamines of the 1st generation (antazoline, bromadryl, brompheniramine, dithiaden, cyclizine, chlorcyclizine, chlorpheniramine, clemastine) and the 2nd generation (acrivastine, ketotifen, and loratadine) on the respiratory burst of phagocytes. Reactive oxygen species generation in neutrophils isolated from rat blood was measured using luminol-enhanced chemiluminescence. Changes in nitrite formation and iNOS protein expression by RAW 264.7 macrophages were analysed using Griess reaction and Western blotting. The antioxidative properties of drugs in cell-free systems were detected spectrophotometrically, luminometrically, fluorimetrically, and amperometrically. The majority of the H1-antihistamines tested (bromadryl, brompheniramine, chlorcyclizine, chlorpheniramine, clemastine, dithiaden, and ketotifen) exhibited a significant inhibitory effect on the chemiluminescence activity of phagocytes. H1-antihistamines did not show significant scavenging properties against superoxide anion and hydroxyl radical, thus this could not contribute to the inhibition of chemiluminescence. H1-antihistamines had a different ability to modulate nitric oxide production by LPS-stimulated macrophages. Bromadryl, clemastine, and dithiaden were the most effective since they inhibited iNOS expression, which was followed by a significant reduction in nitrite levels. H1-antihistamines had no scavenging activity against nitric oxide. It can be concluded that the effects observed in the H1-antihistamines tested are not mediated exclusively via H1-receptor pathway or by direct antioxidative properties. Based on our results, antihistamines not interfering with the microbicidal mechanisms of leukocytes (antazoline, acrivastine and cyclizine) could be used preferentially in infections. Other antihistamines should be used, under pathological conditions accompanied by the overproduction of reactive oxygen species.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Bakker RA Schoonus SB Smit MJ Timmerman H Leurs R. (2001). Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gammaand G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 60: 1133-1142.

  • Church MK. (2001). H(1)-antihistamines and inflammation. Clin Exp Allergy 31: 1341-1343.

  • Číž M Čížova H Denev P Kratchanova M Slavov A Lojek A. (2010). Different methods for control and comparison of the antioxidant properties of vegetables. Food Control 21: 518-523.

  • Číž M Komrsková D Prachařová L Okénková K Čížová H Moravcová A Jančinová V Petríková M Lojek A Nosáľ R. (2007). Serotonin modulates the oxidative burst of human phagocytes via various mechanisms. Platelets 18: 583-590.

  • De Vos C. (1999). H1-receptor antagonists: effects on leukocytes myth or reality? Clin Exp Allergy 29: 60-63.

  • Drábiková K Nosáľ R Jančinová V Číž M Lojek A. (2002). Reactive oxygen metabolites production is inhibited by histamine and H1-antagonist dithiaden in human PMN-leukocyte. Free Radical Res 36 975-980.

  • Králová J. Račková L Pekarová M Kubala L Nosáľ R Jančinová V Číž M Lojek A. (2009). The effects of H1-antihistamines on the nitric oxide production by RAW 264.7 cells with respect to their lipophilicity. Int Immunopharmacol 9: 990-995.

  • Leurs R Smit MJ Timmerman H. (1995). Molecular pharmacological aspects of histamine receptors. Pharmacol Ther 66: 413-463.

  • Moncada S Higgs A. (1993). The L-arginine-nitric oxide pathway. N Engl J Med 329: 2002-2012.

  • Nosáľ R Jančinová V Číž M Drábiková K Lojek A Fábryová V. (2005). Inhibition of chemiluminescence by carvedilol in the cell-free system whole human blood and blood cells. Scand J Clin Lab Invest 65 55-64.

  • Pavelková M Kubala L. (2004). Luminol- isoluminol- and lucigenin-enhanced chemiluminescence of rat blood phagocytes stimulated with different activators. Luminescence 19: 37-42.

  • Pekarová M Králová J Kubala L Číž M Lojek A Gregor Č Hrbáč J. (2009). Continuous electrochemical monitoring of nitric oxide production in murine macrophage cell line RAW 264.7. Anal Bioanal Chem 394: 1497-1504.

  • Tiligada E Zampeli E Sander K Stark H. (2009). Histamine H3 and H4 receptors as novel drug targets. Expert Opin Investig Drugs 18: 1519-1531.

  • Yang EJ Yim EY Song G Kim GO Hyun CG. (2009). Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages by Jeju plant extracts. Interdiscip Toxicol 2: 245-249.

Journal information
Impact Factor

CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1031 958 10
PDF Downloads 984 965 2