Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells

T. Nakashima, E. Sato, Y. Niwano, M. Kohno, W. Muraoka, T. Oda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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. Objectives: 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 264·7 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.

Original languageEnglish
Pages (from-to)720-727
Number of pages8
JournalBritish Journal of Dermatology
Volume156
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

Keywords

  • Antifungal agent
  • Inflammatory cells
  • NADPH oxidase
  • Reactive oxygen species
  • Seborrhoeic dermatitis

ASJC Scopus subject areas

  • Dermatology

Fingerprint Dive into the research topics of 'Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells'. Together they form a unique fingerprint.

  • Cite this