| Project/Area Number |
21590603
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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 |
Applied pharmacology
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| Research Institution | Osaka Ohtani University |
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Principal Investigator |
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| Research Collaborator |
YAMAGATA Masayo 大阪大谷大学, 薬学部, 講師 (50454583)
TSUTSUI Hidenobu 大阪大谷大学, 薬学部, 助教 (30434806)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 薬物治療学 / 急性腎不全 / 腎虚血再灌流障害 / ノルエピネフリン / 活性酸素種 / モノアミンオキシターゼ / 慢性腎臓病 |
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| Research Abstract |
We have found that increases in renal sympathetic nerve activity during ischemic period and renal venous norepinephrine(NE) level after reperfusion play important roles in the development of ischemia/reperfusion(I/R)-induced acute kidney injury. In the present study, we examined the effect of isatin, an endogenous monoamine oxidase(MAO) inhibitor, moclobemide, a selective MAO_A inhibitor, and selegiline, a selective MAO_B inhibitor, on renal venous NE levels, superoxide(O_2^-) production after reperfusion and I/R-induced acute kidney injury. I/R-induced acute kidney injury was made by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Injection of isatin or moclobemide before ischemia increased the renal venous plasma NE level after reperfusion and aggravated I/R-induced renal injury, but not selegiline administration. The excessive O_2^-production after reperfusion was significantly suppressed by injection of all drugs, indicating that the inhibition of oxidative deamination effectively suppressed O_2^-production. Therefore, the aggravation effect of isatin seems to be mediated through increased NE levels in the kidney after reperfusion on I/R-induced acute kidney injury.
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