1993 Fiscal Year Final Research Report Summary
Infarct-Limiting Effect of gamma-glutamylcysteine Ethyl Ester in a Cnine Occlusion-Reperfusion Model
| Project/Area Number |
04670534
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
HOSHIDA Shiro Osaka University, School of Medicine Assistant, 医学部, 助手 (80238732)
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| Co-Investigator(Kenkyū-buntansha) |
KUZUYA Tsunehiko Osaka University, School of Medicine Assosiate Professor, 医学部, 助教授 (80150340)
TADA Michihiko Osaka University, School of Medicine Professor, 医学部, 教授 (90093434)
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| Project Period (FY) |
1992 – 1993
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| Keywords | gultathione / infarct size / reperfusion / myeloperoxidase / 白血球 |
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| Research Abstract |
Since gamma-glutamylcysteine ethyl ester (TEI12306), a precursor of reduced glutathione (GSH) biosynthesis, can penetrate into cells in tis intact-form and then be converted to GSH by GSH synthetase, we ezamined infarct-limiting effect of this agent in open-chest dogs subjected to 90-minute coronary occlusion followed by 5 hours of reperfusion.
Administration of TEI 2306 (3.10mg/kg, iv) immediately before reperfusion showed reduction of infarct size in a dose dependent manner, while no differences were seen in hemodynamic parameters and regional myocardial blood flow during the ischemic period and after reperfusion between control and pretreated dogs. Reduction of GSH content in the ischemic myocardium and increase in transcardiac release of oxidized glutathinone (GSSG) after reperfusion were significantly suppressed by the trreatment. Under these conditions, myeloperoxidase (MPO) activity in the ischemic myocardium was also suppressed. These results indicate that TEI 2306 significantly attenuates myocardial ischemia/reperfusion injury through preservation of myocardial GSH content.
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