Modulation of metabolic activity of phagocytes by antihistamines

LOJEK, Antonín, Milan ČÍŽ, Michaela PEKAROVÁ, Gabriela AMBROŽOVÁ, Ondřej VAŠÍČEK, Jana MORAVCOVÁ, Lukáš KUBALA, Drábíková KATARÍNA, Jančinová VIERA, Perečko TOMÁŠ, Pečivová JANA, Mačičková TATIANA a Nosál RADOMÍR. Modulation of metabolic activity of phagocytes by antihistamines. Interdisciplinary Toxicology. 2011. ISSN 1337-6853. Dostupné z: https://dx.doi.org/10.2478/v10102-011-0004-z.

Základní údaje

• Originální název: Modulation of metabolic activity of phagocytes by antihistamines
• Autoři: LOJEK, Antonín, Milan ČÍŽ, Michaela PEKAROVÁ, Gabriela AMBROŽOVÁ, Ondřej VAŠÍČEK, Jana MORAVCOVÁ, Lukáš KUBALA, Drábíková KATARÍNA, Jančinová VIERA, Perečko TOMÁŠ, Pečivová JANA, Mačičková TATIANA a Nosál RADOMÍR.
• Vydání: Interdisciplinary Toxicology, 2011, 1337-6853.

Další údaje

• Typ výsledku: Článek v odborném periodiku
• Utajení: není předmětem státního či obchodního tajemství
• Doi: http://dx.doi.org/10.2478/v10102-011-0004-z

Anotace

The purpose of the study was to investigate the effects of H(1)-antihistamines of the 1(st) generation (antazoline, bromadryl, brompheniramine, dithiaden, cyclizine, chlorcyclizine, chlorpheniramine, clemastine) and the 2(nd) 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 H(1)-antihistamines tested (bromadryl, brompheniramine, chlorcyclizine, chlorpheniramine, clemastine, dithiaden, and ketotifen) exhibited a significant inhibitory effect on the chemiluminescence activity of phagocytes. H(1)-antihistamines did not show significant scavenging properties against superoxide anion and hydroxyl radical, thus this could not contribute to the inhibition of chemiluminescence. H(1)-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. H(1)-antihistamines had no scavenging activity against nitric oxide. It can be concluded that the effects observed in the H(1)-antihistamines tested are not mediated exclusively via H(1)-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.

Anotace anglicky

The purpose of the study was to investigate the effects of H(1)-antihistamines of the 1(st) generation (antazoline, bromadryl, brompheniramine, dithiaden, cyclizine, chlorcyclizine, chlorpheniramine, clemastine) and the 2(nd) 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 H(1)-antihistamines tested (bromadryl, brompheniramine, chlorcyclizine, chlorpheniramine, clemastine, dithiaden, and ketotifen) exhibited a significant inhibitory effect on the chemiluminescence activity of phagocytes. H(1)-antihistamines did not show significant scavenging properties against superoxide anion and hydroxyl radical, thus this could not contribute to the inhibition of chemiluminescence. H(1)-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. H(1)-antihistamines had no scavenging activity against nitric oxide. It can be concluded that the effects observed in the H(1)-antihistamines tested are not mediated exclusively via H(1)-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.