Publication details

Effect of carvedilol on the production of reactive oxygen species by HL-60 cells

Authors

LOJEK Antonín PEČIVOVÁ Jana MACICKOVA T NOSÁL Radomír PAPEŽÍKOVÁ Ivana ČÍŽ Milan

Year of publication 2008
Type Article in Periodical
Magazine / Source Neuroendocrinology Letters
Citation
Keywords carvedilol; HL-60 cells; reactive oxygen species; chemiluminescence; antioxidative properties
Description OBJECTIVES: The generation of reactive oxygen species (ROS) by phagocytes is one of the irreplaceable microbicidal tools of innate immunity. It has been reported in our previous studies that short-term treatment by carvedilol ex vivo inhibits ROS generation. The purpose of this study was to investigate the long-term effect of carvedilol on phagocytes. METHODS: Human leukemia HL-60 cells differentiated into granulocyte-like cells were used as the model. Final concentrations of carvedilol were 0.1-100 mu mol/l. The production of ROS by HL-60 cells was measured using luminol-enhanced chemiluminescence (CL). RESULTS: Carvedilol in concentrations 0.1-10 mu mol/l did not exhibit any toxic effect on cells (measured using bioluminescent bacteria Photorhabdus luminescens subsp. thracensis). One hour's treatment with 10 mu mol/l carvedilol significantly decreased both spontaneous and activated CL of cells. Conversely, no inhibitory effects on CL were observed in 10 mu mol/l carvedilol after 48 h incubation; lower concentrations of carvedilol even slightly increased the CL activity of HL-60 cells. A significant increase in spontaneous CL activity was detected in cells incubated with 10 mu mol/l carvedilol in comparison with the control. Powerful antioxidative properties of carvedilol against peroxyl radical (ORAC assay) were proved. No scavenging of nitric oxide (electrochemical method) was observed. CONCLUSIONS: Long-term influence of carvedilol can induce an increase in the generation of phagocyte-derived ROS and potentially also other inflammatory mediators. The increased ROS production is compensated for by antioxidative properties of carvedilol although the increased production of inflammatory mediators could affect the proper function of immune system.

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