title: 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.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Akamatsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Miki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Moataz
authors.initials: M
authors.lastname: Mekawy
authors.forename: Keiji
authors.initials: K
authors.lastname: Hasumi
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology*; D013191:Stachybotrys / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D005343:Fibrinolytic Agents; D011760:Pyrrolidinones; D017382:Reactive Oxygen Species; C409191:SMTP 7; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D020780:Matrix Metalloproteinase 9