| Project/Area Number |
06671038
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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 |
内分泌・代謝学
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| Research Institution | Nagasaki University |
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Principal Investigator |
AKAZAWA Shoichi The First Department of Internal Medicine, School of Medicine Nagasaki University, Lecturer, 医学部, 講師 (10145261)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takahito Department of pathological Biochemistry, Atomic disease institute, School of Med, 医学部, 教授 (00158908)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | embryo culture / glutathione / free radical / hyperglycemia / antioxidant system / scavenger system / フリーラジカル / 高血糖 / 胎仔 |
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| Research Abstract |
We have shown that the mechanism of hyperglycemia-induced embryonic malformations is mediated through increaced free radical formations and glutathione (GSH) depletion in embryo during the critical periods of organogenesis (Diabetes 44 : 992-998,1995).
We investigated effect of GSH-ester administration on diabetes-induced embryonic malformations. Embryos from streptozotocin-induced diabetic pregnant rats showed increased frequency of embryonic malformations (21.2 vs 2.2%, p<0.01). Free radical formations increased in isolated embryonic cells taken from diabetic pregnant rats. The concentration of GSH in embryos from diabetic pregnant rats was significantly decreased compared with normal pregnant rats. The activities of gamma-glutamyl systein synthetase (gamma-GCS), the rate-limiting GSH synthesizing enzyme, in embryos from pregnant diabetic rat did not significantly increased against oxidative stress. To test hypothesis that GSH depletion in crucial role on diabetes-induced malformations, GSH ester was administered intraperitoneally in diabetic pregnant rats during gestational days 6-11. Administration of GSH ester to pregnant diabetic rats restored GSH concentrations in these embryos and reduced free radical species leading to reduced incidence of embryonic malformations (1.1 vs 21.2%, p<0.01). These results indicate that an embryo during main periods of organogenesis, GSH depletion and impaired response of GSH synthesizing enzyme despite oxidative stress has crucial role in embryonic malformation in deabetic pregnancy.
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