The effect of antihistamines drugs on the functional activity of neutrophils

Abstract

Allergic inflammation is accompanied by stimulation of neutrophils with an increase in the formation of reactive oxygen species. The antioxidant effectiveness of some antihistamines is known, which reduces the risk of damage to surrounding tissues with the participation of these cells. Objective of the study: to determine the degree of various generations antihistamines influence on the death and enzymatic activity of neutrophils. The effect of the first antihistamines (diphenhydramine, clemastine) and second (lorata-dine, desloratadine) generations and the hormonal drug dexameth-asone on cell viability, the formation of active oxygen metabolites, enzyme activity, the amount of cationic proteins, and cytokine production by neutrophils was studied using the in vitro model. It was found that after exposure to loratadine at a dose of 2.5 |jg / ml, the number of viable cells was comparable (p = 0.001) with that in an intact culture. Found a stimulating effect of second generation antihistamines (loratadine, desloratadine) in low doses on the activity of NADPH-dependent oxide reductase. The form of neutrophil death depended on the type and dose of the drug; apoptosis was predominantly observed after cell contact with loratadine and desloratadine. Against the background of an increase in the activity of ATPase and myeloperoxidase after contact with diphenhydramine and clemastine (2.5 jg / ml), the largest number of neutrophils producing reactive oxygen species was revealed. Under the influence of desloratodine and clemastine, exocytosis of cationic proteins into the extracellular space and the lowest production of cytokines after contact with the latter were established. Thus, exposure to Hl-antihistamines, active both extra- and intracellular (diphenhydramine, loratadine), probably disrupted the metabolism of neutrophils, which led to an increase in their killer potential. Clemastine, acting mainly extracellularly, minimized the toxic effects of extracellular radicals, without affecting the production of intracellular oxidants involved in the regulation of neutrophil functions.