Analysis of the metabolic disorder based on the redox theory in the septic patient induced by nitric oxide
| Project/Area Number |
10671227
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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 |
Digestive surgery
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| Research Institution | KANSAI MEDICAL UNIVERSITY |
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Principal Investigator |
KANEMAKI Toshiki KANSAI MEDICAL UNIVERSITY, THE 1ST DEPARTMENT OF SURGERY, RESEARCH ASSOCIATE, 医学部, 助手 (40278619)
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| Co-Investigator(Kenkyū-buntansha) |
KITADE Hiroaki KANSAI MEDICAL UNIVERSITY, THE 1ST DEPARTMENT OF SURGERY, RESEARCH ASSOCIATE, 医学部, 助手 (20298855)
KOWN A-hon KANSAI MEDICAL UNIVERSITY, THE 1ST DEPARTMENT OF SURGERY, ASSOCIATE PROFESSOR, 医学部, 助教授 (70225605)
松井 陽一 関西医科大学, 医学部, 助手 (60278637)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | Nitric Oxide / NO analyzer / ketore body ratio / redox theory / hepatocyte / liver dysfunction / primary culture / sepsis |
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| Research Abstract |
Nitric oxide (NO) production in primary cultured rat hepatocytes were observed for 2 hours using the NO monitor. These findings were the same as nitrite measured by Griess reagent method. However, after 2 hours, we would not detected the NO. The attachment of the hepatocytes to the NO monitor affected the measurement.
Nitric oxide production and its effect on energy metabolism was investigated in cultured rat hepatocytes obtained from the liver remnant after partial hepatectomy. The hepatocytes obtained from liver remnant after partial hepatectomy (HPH) produced more nitric oxide than hepatocytes obtained from sham operated liver (HS), following stimulation with IL-1β. In our recent study, IL-1β was shown to stimulate nitric oxide (NO) production in cultured rat hepatocytes and NO reduced the ketone body ratio (KBR : acetoacetate/b-hydroxybutyrate). The reduced KBR, reflecting the liver mitochondrial redox state (NADィイD1+ィエD1/NADH), resulted in the inhibition of ATP synthesis. In the present study, KBR in the medium of cultured HPH was lower than that of HS. Furthermore, adenine nucleotides content (ATP, ADP and AMP) was lower in HPH than in HS. These results suggest that following partial hepatectomy, the liver is more susceptible to mitochondrial dysfunction as a result of the nitric oxide produced during infection. The similar results ware observed in hepatocytes obtained from obstructive jaudice rat.
In conclusion, hepatocytes in the liver remnant after partial hepatectomy demonstrated increased NO production which was attributed to increased sensitivity to IL-1βNO in turn, cause liver dysfunction after hepatectomy because NO induces hepatic mitochondria dysfunction.
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Report
(3 results)
Research Products
(7 results)
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[Publications] Satoi S and Kitade H, Hiramatsu Y, Kwon A-H, Takahashi H, Sekiguchi K, Uehara M, Oda M, Yanagimoto Y, Miyashita K, Sakashita E, Kamiyama Y: "Increased Extra Domain-A Containing Fibronectin and Hepatic Dysfunction During Septic Response 〜in vivo and in vitro Study〜"Shock. (in press).
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