Neurotoxicology
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Oxidative stress is implicated as an important factor in the development of Alzheimer's disease (AD). In the present study, we have investigated the effects of edaravone (9mg/kg, 3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, in a streptozotocin (STZ-3mg/kg) induced rat model of sporadic AD (sAD). Treatment with edaravone significantly improved STZ-induced cognitive damage as evaluated in Morris water maze and step-down tests and markedly restored changes in malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) adducts, hydroxyl radical (OH), hydrogen peroxide (H2O2), total superoxide dismutase (T-SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and protein carbonyl (PC) levels. ⋯ Moreover, hyperphosphorylation of tau resulting from intracerebroventricular streptozotocin (ICV-STZ) injection was decreased by the administration of edaravone. These results provide experimental evidence demonstrating preventive effects of edaravone on cognitive dysfunction, oxidative stress and hyperphosphorylation of tau in ICV-STZ rats. Since edaravone has been used for treatment of patients with stroke, it represents a safe and established therapeutic intervention that has the potential for a novel application in the treatment of age-related neurodegenerative disorders associated with cognitive decline, such as AD.