Journal
NEUROTOXICOLOGY
Volume 38, Issue -, Pages 136-145Publisher
ELSEVIER
DOI: 10.1016/j.neuro.2013.07.007
Keywords
Streptozotocin; Edaravone; Oxidative stress; Tau hyperphosphorylation
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Funding
- Health Department Project of Heilongjiang Province [2011-035]
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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 (9 mg/kg, 3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, in a streptozotocin (STZ-3 mg/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)-O-center dot), hydrogen peroxide (H2O2), total superoxide dismutase (T-SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and protein carbonyl (PC) levels. In addition, histomorphological observations confirmed the protective effect of edaravone on neuronal degeneration. 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. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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