2003 Fiscal Year Final Research Report Summary
Suppression of Ischemia-Reperfusion Myocardial Damage via Enhancement of Repair of Oxidative DNA Damage
| Project/Area Number |
14570630
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
HASEBE Naoyuki Asahikawa Medical College, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30192272)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Ischemia reperfusion injury / Oxidative stress / DNA base injury / Myocardial infarction / Glutathione / Preconditioning / Base excision repair |
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| Research Abstract |
The myocardial infarct size of isolated rabbit hearts undergone 30/60min of ischemia/reperfusion was significantly reduced in 5/10min preconditioned hearts, particularly in the subendocardium. Exogenous H_2O_2 aggravated ischemia/reperfusion injury, particularly in the subepicardium. The reduced form of glutathione levels, but not glutathione peroxidase activities were well preserved transmurally in preconditioned hearts. The serum levels of 8-hydroxydeoxyguanosine(8-OHdG), an indicator of oxidative DNA damage, were increased in ontrol, predominantly in the subendocardium, and it was significantly enhanced in H_2O_2 loading on reperfusion, particularly in the subepicardium(p<0.01). These changes were effectively diminished by preconditioning. The expression of endnuclease assessed by immuno-histochemistry was not significantly affected, but protein levels were detected to be increased at the border-zone of infarction by western blotting. Orally administered ebselene, a glutathione peroxidase like antioxidant exerted pharmacological preconditioning like effect. The enhancement of myocardial damage by H_2O_2 was significantly suppressed by ebselen along with preservation of glutathione and similar reduction in myocardial 8-deoxyguanosme levels. Ebselen markedly enhanced heat shock protein 72(HSP72) expression. A specific HSP inhibitor, KNK437 abolished cardio protective effects of ebselen in cultured myocytes suggesting molecular chaperon mediates cardioprotective effects of ebselen.
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Research Products
(4 results)
