Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats.
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. 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.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: zhouss613008@126.com.
Shanshan
S
Zhou
Guichun
G
Yu
Lijun
L
Chi
Jiwei
J
Zhu
Wei
W
Zhang
Yan
Y
Zhang
Liming
L
Zhang
D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D057967:Infusions, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013311:Streptozocin / Q000008:administration & dosage*; D016875:tau Proteins / Q000378:metabolism*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D016875:tau Proteins; D013311:Streptozocin; D000077553:Edaravone; D000983:Antipyrine
Edaravone; Oxidative stress; Streptozotocin; Tau hyperphosphorylation