Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells.
BACKGROUND
Reactive oxygen species (ROS) released from inflammatory cells constitute one of the critical causative factors in inflammatory skin diseases such as seborrhoeic dermatitis and atopic dermatitis.


OBJECTIVE
To investigate inhibitory effects of ketoconazole (KCZ) and ciclopiroxolamine (CPO), both of which have been used for the treatment of seborrhoeic dermatitis, on ROS released from inflammatory cells.


METHODS
The methyl-Cypridina-luciferin analogue-dependent chemiluminescence method was employed for the detection of ROS production by phorbol 12-myristate 13-acetate (PMA)-stimulated inflammatory cells. Moreover, the radical scavenging activities of both agents were examined by using a hypoxanthine-xanthine oxidase system and the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). NADPH oxidase activity was determined in particulate (membrane) fractions prepared from PMA-stimulated RAW 264 x 7 cells, a macrophage-like cell line.


RESULTS
Both of these antifungal agents inhibited PMA-stimulated ROS production. However, only CPO significantly scavenged both ROS generated by the hypoxanthine-xanthine oxidase system and DPPH, and the scavenging activity of CPO seemed to act on ROS other than superoxide anions. Although KCZ inhibited PMA-stimulated ROS production, it did not show radical-scavenging activities. The inhibition of ROS production by KCZ is probably attributable to the inhibition of NADPH oxidase activity.


CONCLUSIONS
The mechanism of the inhibitory action of KCZ against PMA-stimulated ROS production is distinct from that of CPO. Knowledge of the inhibitory or scavenging effects of both antifungal agents on ROS released from inflammatory cells may be useful in developing a therapeutic strategy for dermatitis.
Nakashima
T
T
NITE Biological Research Center (NBRC), National Institute of Technology and Evaluation, Chiba, Japan. takuji.nakashima@nifty.com
Sato
E
E
Niwano
Y
Y
Kohno
M
M
Muraoka
W
W
Oda
T
T
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000077768:Ciclopirox; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology*; D051379:Mice; D011728:Pyridones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome; D014969:Xanthine Oxidase / Q000172:deficiency
D000935:Antifungal Agents; D004338:Drug Combinations; D011728:Pyridones; D017382:Reactive Oxygen Species; D000077768:Ciclopirox; D014969:Xanthine Oxidase; D007654:Ketoconazole