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Abstract
Oxygen free radicals have been proposed to be major causative agents in secondary brain damage in traumatic and ischemic brain injury. Edarabone (3-methyl-1-phenyl-2-pyrazolin-5-one), a powerful antioxidative radical scavenger, is the only drug currently available in clinical practice for the treatment of cerebral infarction. There has been increasing interest in the role of nitric oxide (NO•) as a causative agent in brain injury. In the present study, we investigated the scavenging effect of Edarabone on nitric oxide (NO•), using an electron spin resonance (ESR) method. NO• was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy (carboxy-PTI) produced from the reaction between 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (carboxy-PTIO) and NO•. Edarabone directly scavenged NO• in a dose-dependent manner. These ESR studies indicate that Edarabone has a direct NO• scavenging activity and the additional possibility of novel neuroprotective activities against brain injury and focal cerebral ischemia.
