The effects of H-1-antihistamines on the nitric oxide production by RAW 264.7 cells with respect to their lipophilicity

Časopis: INTERNATIONAL IMMUNOPHARMACOLOGY 9, 990-995
Autoři: Kralova, J., Rackova, L., Pekarova, M., Kubala, L., Nosal', R., Jancinova, V., Ciz, M., Lojek, A.
Rok: 2009

Abstrakt

H-1-antihistamines are known to be important modulators of inflammatory response. However, the information about the influence of these drugs on reactive nitrogen species generation is still controversial. The main aim of the present study was to investigate the effects of selected H-1-antihistamines on nitric oxide production by lipopolysaccharide-stimulated murine macrophages RAW 264.7, measured as changes in inducible nitric oxide synthase (iNOS) protein expression in cell lysates by Western blotting and nitrite formation in cell supernatants using the Griess reaction. In pharmacological non-toxic concentrations, H-1-antihistamines significantly inhibited nitrite accumulation that was not caused by the scavenging ability of drugs against nitric oxide, measured amperometrically. The degree of inhibition of nitrite accumulation positively correlated with the degree of tested lipophilicity, measured by reversed-phase thin layer chromatography. Furthermore, H-1-antihistamines differentially modulated the iNOS protein expression. In conclusion, as was shown in this study, the modulation of nitric oxide production could be caused by the downregulation of iNOS protein expression and/or the iNOS protein activity. (C) 2009 Elsevier B.V. All rights reserved.