SP-8203 reduces oxidative stress via SOD activity and behavioral deficit in cerebral ischemia.

Abstract

Both oxidative stress and excessive activation of glutamate receptors are implicated as major causes of ischemic brain injury. However, the existing N-methyl-D-aspartate (NMDA) receptor antagonists have not exerted good clinical outcome, most likely because they do not protect neurons against oxidative stress. Thus, more effective glutamate antagonists and antioxidants are needed for the treatment of ischemic stroke. In previous study, SP-8203, derived from earth worms, showed the blocking effect of NMDA receptor. We provided evidence that SP-8203 could also suppress the oxidative stress in this study. In vitro, 250 μM H2O2 was treated to SH-SY5Y cells after the pre-treatment of SP-8203 (2, 20 and 200 μM). SP-8203 significantly suppressed H2O2-induced cell death and reactive oxygen species production. In addition, we investigated the effects of SP-8203 in middle cerebral artery (MCA) occluded rat model. SP-8203 (5 and 10 mg/kg) was administered intraperitoneally to rats before and after the MCA occlusion and was injected daily for 10 days. After 10 days, SP-8203 remarkably reduced brain infarct volume and lipid peroxidation products in the MCA-occluded rats but MK-801 didn't. Moreover, SP-8203 significantly improved neurological deficits such as shortening of latency time in Rota rod performance. However, MK-801 didn't improve behavioral deficits. Therefore, SP-8203 may be more effective for multiple-target mechanisms of ischemic stroke.

• Authors: Su-Jin Noh, Sang Hyung Lee, Ki Young Shin, Chul Kyu Lee, Il Hwan Cho, Hye-Sun Kim, Yoo-Hun Suh
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 98 Issue 1 Pg. 150-4 (Mar 2011) ISSN: 1873-5177 [Electronic] United States
• PMID: 21172384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Acetamides
• Antioxidants
• Neuroprotective Agents
• Quinazolinones
• Glutamic Acid
• Dizocilpine Maleate
• Hydrogen Peroxide
• Superoxide Dismutase
• otaplimastat

Topics

• Acetamides
• Animals
• Antioxidants (pharmacology)
• Behavior, Animal (drug effects)
• Brain Ischemia (drug therapy, metabolism, psychology)
• Cell Death (drug effects)
• Cell Line
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Glutamic Acid (toxicity)
• Humans
• Hydrogen Peroxide (toxicity)
• Lipid Peroxidation (drug effects)
• Male
• Motor Activity (drug effects)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Quinazolinones (pharmacology)
• Rats
• Rats, Wistar
• Superoxide Dismutase (metabolism)