| Project/Area Number |
11670025
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
SUMI Yawara St.Marianna University School of Medicine, Department of Medicine, professor, 医学部, 教授 (20121197)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Masayuki St.Marianna University School of Medicine, Department of Medicine, assistant professor, 医学部, 講師 (10198898)
YOSHIDA Minoru St.Marianna University School of Medicine, Department of Medicine, associate professor, 医学部, 助教授 (80081660)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | melatonin / cisplatin / oxidative stress / 6-hydroxymelatonin / glutathione peroxidase / renal function / 活性酸素 / スカベンジャー / in vitro / ラット / グルタチオン / 脂質過酸化物 / 腎障害 |
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| Research Abstract |
In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline was administered intraperitoneally (i.p.) to male Sprague-Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals received each indolamine or saline every day and were sacrificed three or five days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone ; these values decreased significantly with melatonin co-treatment of CP treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were
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treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP enhanced lipid peroxidation in kidney ; again, this was prevented in animals treated with melatonin. The activity of the antioxidant enzyme glutathione peroxidase decreased as a result of CP administration, which were restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats ; these changes were prevented by melatonin treatment. 6-OHM was shown to have some antioxidative capacity ; however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin cotreated rats was significantly lower than that of CP treated only rats. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP.This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function. Less
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