EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology.

Abstract

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.

• Authors: Y Rong, S R Doctrow, G Tocco, M Baudry
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 17 Pg. 9897-902 (Aug 17 1999) ISSN: 0027-8424 [Print] United States
• PMID: 10449791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Spectrin
• 3-nitrotyrosine
• Tyrosine
• Catalase
• Superoxide Dismutase
• Kainic Acid

Topics

• Animals
• Catalase (metabolism)
• Electrophoresis, Polyacrylamide Gel
• Kainic Acid (toxicity)
• Molecular Mimicry
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Spectrin (metabolism)
• Superoxide Dismutase (metabolism)
• Tyrosine (analogs & derivatives, analysis)