Osamu Tokumaru1, Yachiko Shuto2, Kazue Ogata3, Masato Kamibayashi4, Kira Bacal5, Hidehiro Takei6, Isao Yokoi7, Takaaki Kitano3. 1. Faculty of Welfare and Health Sciences, Oita University, Oita City, Oita Pref., Japan. Electronic address: ostokuma@oita-u.ac.jp. 2. Department of Neurophysiology, Oita University Faculty of Medicine, Yufu City, Oita Pref., Japan; Nursing School, Beppu University, Beppu City, Oita Pref., Japan. 3. Department of Anesthesiology, Oita University Faculty of Medicine, Yufu City, Oita Pref., Japan. 4. Kyoto Pharmaceutical University, Kyoto City, Kyoto Pref., Japan. 5. Medical Programme Directorate, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. 6. Department of Pathology, The Methodist Hospital, Houston, Texas. 7. Department of Neurophysiology, Oita University Faculty of Medicine, Yufu City, Oita Pref., Japan.
Abstract
BACKGROUND: Edaravone is a powerful free radical scavenger that is in clinical use. However, data concerning its dose-response relationship against multiple free radicals remain sparse. The purpose of the present study was to demonstrate the dose-dependency of direct scavenging activity of edaravone against multiple free radical species. MATERIALS AND METHODS: Free radical-scavenging activities of edaravone against six free radical species were evaluated by electron spin resonance spectroscopy using spin-trapping method. RESULTS: Edaravone scavenged the following free radicals in dose-dependent manners with reaction rate constants (kedaravone) or 50% inhibitory concentration (IC50) as indicated: hydroxyl radical (kedaravone = 5.2 × 1010 M-1 s-1), superoxide anion (kedaravone/kG-CYPMPO = 0.63), tert-butyl peroxyl radical (kedaravone/kG-CYPMPO = 8.8), ascorbyl free radical (IC50 = 0.17 ± 0.06 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 4.7 ± 0.3 μM), and nitric oxide (kedaravone = 7.0 × 103 M-1 s-1). CONCLUSIONS: The dose-dependent scavenging activities of edaravone against multiple free radical species were clearly illustrated. It is speculated that edaravone acts as antioxidant by dose-dependently scavenging multiple free radical species along the chain reactions of oxidative stress in surgery.
BACKGROUND:Edaravone is a powerful free radical scavenger that is in clinical use. However, data concerning its dose-response relationship against multiple free radicals remain sparse. The purpose of the present study was to demonstrate the dose-dependency of direct scavenging activity of edaravone against multiple free radical species. MATERIALS AND METHODS:Free radical-scavenging activities of edaravone against six free radical species were evaluated by electron spin resonance spectroscopy using spin-trapping method. RESULTS:Edaravone scavenged the following free radicals in dose-dependent manners with reaction rate constants (kedaravone) or 50% inhibitory concentration (IC50) as indicated: hydroxyl radical (kedaravone = 5.2 × 1010 M-1 s-1), superoxide anion (kedaravone/kG-CYPMPO = 0.63), tert-butyl peroxyl radical (kedaravone/kG-CYPMPO = 8.8), ascorbyl free radical (IC50 = 0.17 ± 0.06 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 4.7 ± 0.3 μM), and nitric oxide (kedaravone = 7.0 × 103 M-1 s-1). CONCLUSIONS: The dose-dependent scavenging activities of edaravone against multiple free radical species were clearly illustrated. It is speculated that edaravone acts as antioxidant by dose-dependently scavenging multiple free radical species along the chain reactions of oxidative stress in surgery.