EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology.
The present study tested the effects of EUK-134, a synthetic superoxide dismutase/catalase mimetic, on several indices of oxidative stress and neuropathology produced in the rat limbic system as a result of seizure activity elicited by systemic kainic acid (KA) administration. Pretreatment of rats with EUK-134 did not modify the latency for or duration of KA-induced seizure activity. It did produce a highly significant reduction in increased protein nitration, activator protein-1- and NF-kappaB-binding activity, and spectrin proteolysis as well as in neuronal damage resulting from seizure activity in limbic structures. These results support the hypothesis that kainate-induced excitotoxicity is caused, at least in part, by the action of reactive oxygen species. Furthermore, they suggest that synthetic superoxide dismutase/catalase mimetics such as EUK-134 might be used to prevent excitotoxic neuronal injury.
Rong
Y
Y
Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520, USA.
Doctrow
S R
SR
Tocco
G
G
Baudry
M
M
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007608:Kainic Acid / Q000633:toxicity*; D018716:Molecular Mimicry; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D017382:Reactive Oxygen Species; D013049:Spectrin; C002744:3-nitrotyrosine; D014443:Tyrosine; D002374:Catalase; D013482:Superoxide Dismutase; D007608:Kainic Acid