Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells
- 21 December 2006
- journal article
- Published by Oxford University Press (OUP) in British Journal of Dermatology
- Vol. 156 (4), 720-727
- https://doi.org/10.1111/j.1365-2133.2006.07655.x
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.Keywords
This publication has 35 references indexed in Scilit:
- MfLIP1, a gene encoding an extracellular lipase of the lipid-dependent fungus Malassezia furfurMicrobiology, 2006
- REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal TransductionAnnual Review of Plant Biology, 2004
- Cross-Talk between the Pathways Leading to the Induction of Apoptosis and the Secretion of Tumor Necrosis Factor- in Ricin-Treated RAW 264.7 CellsThe Journal of Biochemistry, 2003
- Is There a Relation between Risk Groups or Initial CD4 T Cell Counts and Prevalence of Seborrheic Dermatitis in HIV-Infected Patients?Dermatology, 1999
- Is seborrhea a sign of autonomic impairment in Parkinson's disease?Journal of Neural Transmission, 1997
- Oxidant scavenger function of ambroxol in vitro: a comparison with N-acetylcysteineZeitschrift für Die Gesamte Experimentelle Medizin, 1997
- Selective calmodulin antagonists fail to inhibit phorbol ester-induced superoxide anion release from human neutrophils: effects of antifungal azole derivativesBritish Journal of Dermatology, 1996
- Tissue Destruction by NeutrophilsNew England Journal of Medicine, 1989
- The production of hydroxyl and superoxide radicals by stimulated human neutrophils — measurements by EPR spectroscopyFEBS Letters, 1979
- The use of acetylated ferricytochrome C for the detection of superoxide radicals produced in biological membranesBiochemical and Biophysical Research Communications, 1975