Effect of carvedilol on the production of reactive oxygen species by HL-60 cells.
OBJECTIVE
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 micromol/l. The production of ROS by HL-60 cells was measured using luminol-enhanced chemiluminescence (CL).


RESULTS
Carvedilol in concentrations 0.1-10 micromol/l did not exhibit any toxic effect on cells (measured using bioluminescent bacteria Photorhabdus luminescens subsp. thracensis). One hour's treatment with 10 micromol/l carvedilol significantly decreased both spontaneous and activated CL of cells. Conversely, no inhibitory effects on CL were observed in 10 micromol/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 micromol/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.
Lojek
Antonin
A
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic. alojek@ibp.cz
Pecivova
Jana
J
Macickova
Tatiana
T
Nosal
Radomir
R
Papezikova
Ivana
I
Ciz
Milan
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000633:toxicity; D002227:Carbazoles / Q000494:pharmacology* / Q000633:toxicity; D000077261:Carvedilol; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005470:Fluorometry; D006098:Granulocytes / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D049449:Luminescence; D009569:Nitric Oxide / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D010545:Peroxides; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D009569:Nitric Oxide; D000255:Adenosine Triphosphate