The effects of lidocaine on superoxide production and p47 Phox translocation in opsonized zymosan-activated neutrophils.
Superoxide is generated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that exists in the cell membrane of neutrophils and contains p47 phox in the enzyme complex. Superoxide is closely related to various diseases, including infection, myocardial infarction, and aspiration pneumonia. Therefore we performed this study to establish how lidocaine acts on NADPH oxidase. We examined the effects of lidocaine on superoxide production in neutrophils using the method of 2-methyl-6-phenyl-3,7-dihydro [1,2-a] pyrazin-3-one (CLA phenyl)-dependent chemiluminescence activated by opsonized zymosan (OZ). Treatment with lidocaine 15 microM suppressed OZ-activated CLA phenyl-dependent chemiluminescence by approximately 40% compared with that of OZ only-activated neutrophils. It was further demonstrated that the suppressive effect of lidocaine on superoxide production was dependent on the concentration of lidocaine. Translocation of p47 phox from the cytosol to the cell membrane was studied using immunoblot analysis with a polyclonal anti-p47 phox antibody. Lidocaine suppressed OZ-induced p47 phox translocation in a dose-dependent manner. Our results suggest that suppression of superoxide production by a therapeutic dose of lidocaine correlates strongly with suppression of p47 phox translocation.


CONCLUSIONS
We report on the effects of lidocaine on superoxide production in opsonized zymosan-activated neutrophils. Lidocaine suppresses superoxide production in a dose-dependent manner. This suppression correlates strongly with the suppression of translocation of p47 phox, a new subunit of NADPH-oxidase.
Arakawa
K
K
Department of Anesthesiology and Department of Biochemistry, School of Medicine, Nihon University, Tokyo, Japan.
Takahashi
H
H
Nakagawa
S
S
Ogawa
S
S
D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009895:Opsonin Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D000779:Anesthetics, Local; D009895:Opsonin Proteins; D010750:Phosphoproteins; D011719:Pyrazines; C048193:2-methyl-6-phenyl-3,7-dihydroimidazo(1,2-a)pyrazin-3-one; D013481:Superoxides; D015054:Zymosan; D008012:Lidocaine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1