Stachybotrys microspora triprenyl phenol-7, a novel fibrinolytic agent, suppresses superoxide production, matrix metalloproteinase-9 expression, and thereby attenuates ischemia/reperfusion injury in rat brain.

Abstract

Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a novel fibrinolytic agent with anti-inflammatory effect. Previous study demonstrated that SMTP-7 further ameliorated infarction volume in a mouse embolic stroke model compared with tissue type plasminogen activator (tPA), but the reason SMTP-7 has more beneficial effect than tPA has not yet been determined. In the present study, we investigated whether SMTP-7 has an intrinsic neuroprotective effect against transient focal cerebral ischemia (tFCI). Sprague-Dawley rats were subjected to tFCI by intraluminal middle cerebral artery occlusion for 2h. Following induction of tFCI, rats were randomized into two groups based on the agent administered: SMTP-7 group and vehicle group. We examined cerebral infarction volume 24h after reperfusion, and evaluated superoxide production, the expressions of nitrotyrosine and matrix metalloproteinase-9 (MMP-9), which play major roles in secondary brain injury and hemorrhagic transformation. The findings showed that SMTP-7 significantly suppressed superoxide production, the expression of nitrotyrosine and MMP-9 after tFCI, and consequently attenuated ischemic neuronal damage. These results suggest that SMTP-7 has an intrinsic neuroprotective effect on ischemia/reperfusion injury through the suppression of oxidative stress and MMP-9 activation.

• Authors: Yosuke Akamatsu, Atsushi Saito, Miki Fujimura, Hiroaki Shimizu, Moataz Mekawy, Keiji Hasumi, Teiji Tominaga
• Journal: Neuroscience letters (Neurosci Lett) Vol. 503 Issue 2 Pg. 110-4 (Oct 03 2011) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 21871536 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Benzopyrans
• Fibrinolytic Agents
• Pyrrolidinones
• Reactive Oxygen Species
• SMTP 7
• Superoxides
• 3-nitrotyrosine
• Tyrosine
• Matrix Metalloproteinase 9

Topics

• Animals
• Benzopyrans (pharmacology)
• Blotting, Western
• Brain Injuries (drug therapy, enzymology)
• Fibrinolytic Agents (pharmacology)
• Ischemic Attack, Transient (drug therapy, enzymology)
• Male
• Matrix Metalloproteinase 9 (biosynthesis)
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (drug therapy, enzymology)
• Stachybotrys (chemistry)
• Superoxides (metabolism)
• Tyrosine (analogs & derivatives, metabolism)