A free radical scavenger, edaravone, inhibits lipid peroxidation and the production of nitric oxide in hypoxic-ischemic brain damage of neonatal rats.

Abstract

The purpose of this study was to elucidate a role for edaravone, a free radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one, in neonatal hypoxic-ischemic brain damage. We determined the level of thiobarbituric acid reactive substances as an index of lipid peroxidation and nitric oxide metabolites as nitric oxide production. Seven-day-old Wistar rats were subjected to left common carotid artery ligation followed by 2 hours of 8% oxygen exposure. Then, the rats were administered edaravone (9 mg/kg) or saline solution intraperitoneally. Cerebrospinal fluid was withdrawn just before the rats were killed at 2, 5, 24, and 48 hours after hypoxia, and brains were removed. The thiobarbituric acid reactive substances and nitric oxide metabolites levels were measured in the brain tissue and cerebrospinal fluid, respectively. On the ligated side, edaravone significantly decreased thiobarbituric acid reactive substances levels at 5 and 24 hours after hypoxia, compared with saline group (P < .01). Edaravone significantly decreased the nitric oxide metabolites level in the cerebrospinal fluid only at 5 hours, compared with saline group (P < .01). Edaravone potently and transiently inhibited lipid peroxidation and the production of nitric oxide in the neonatal rat brain after hypoxic-ischemic insult.