Effects of edaravone on human neutrophil function.
BACKGROUND
Neutrophils play a crucial role in the antibacterial host defence system. Edaravone is used in critically ill patients who are often immuno-compromised secondary to concomitant disease or immunosuppressive therapy. The aim of the current study was to assess the effect of edaravone, a novel free-radical scavenger, on several aspects of human neutrophil function using an in vitro system.


METHODS
Chemotaxis, phagocytosis, reactive oxygen species (ROS) production by neutrophil (cellular) and xanthine-xanthine oxidase (acellular) systems, and intracellular calcium ion levels ([Ca(2 +) ]i) were measured in the absence and in the presence (at a clinically relevant concentration, and 0.1-fold, and 10-fold this concentration) of edaravone.


RESULTS
The clinically relevant concentration of edaravone did not inhibit chemotxais, phagocytosis, or superoxide production of neutrophils. Even at its ordinary clinical plasma concentration, the drug inhibited hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH*) generation in the cellular (neutrophil) as well as in the cell-free (xanthine-xanthine oxidase) system (P < 0.05). Edaravone did not affect elevation of [Ca(2 +) ]i in neutrophils stimulated by a chemotactic factor.


CONCLUSIONS
These findings suggest that edaravone quenched H(2)O(2), and OH* generated rather than impaired the ability of neutrophils to produce the ROS. However, further studies using in vivo systems are required to elucidate the effects of edaravone on neutrophil function in clinical settings.
Mikawa
K
K
Department of Anesthesia & Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. katzmikawa@yahoo.com
Akamatsu
H
H
Nishina
K
K
Obara
H
H
Niwa
Y
Y
D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000187:drug effects / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D019820:Xanthine; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D000077553:Edaravone; D002118:Calcium; D000983:Antipyrine