1997 Fiscal Year Final Research Report Summary
Research for pathophysiology and therapeutic means of hepatic oxidatiye stress in obstructive iaundice.
| Project/Area Number |
07671424
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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 | Showa University |
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Principal Investigator |
NAKANO Hiroshi Showa University, School of Medicine, Iecturer, 医学部, 講師 (10241035)
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| Co-Investigator(Kenkyū-buntansha) |
KUMADA Kaoru Showa University, School of Medicine, Professor, 医学部, 教授 (00025602)
MIDORIKAWA Takemasa Showa University, School of Medicine, Assistant Professor, 医学部, 助教授 (10255797)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Obstructive jaundice / endotoxin shock / N-acetylcysteine / alpha-glutathione-S-transferase / mitochondrial GSSG / GSH / neutrophil oxidative stress / hepatic microcirculatory flow |
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| Research Abstract |
The aim of the present research was to investigate whether oxidative stress involves in pathophysiologic causes of animals with obstructive jaundice complicating surgical stress.
A cholestatic rat model was produced with ligation of the common bile duct ligation for 2 weeks. Either 5% glucose or N-acetylcysteine (NAC) was administered into abdominal cavity for 2 weeks. Two weeks after bile duct ligation, lipopolysaccharide was administered through the femoral vein. Two hours after administration of lipopolysaccharide, serum concentration of glutathione-S-transferase, which is a reliable marker of hepatocellular injury, was significantly higher in the NAC group than in the 5% glucosegroup. Hepatocellular cytoplasmic concentration of reduced glutathione (GSH) was significantly higher in the NAC group than in the 5% glucose group. Hepatocellular cytoplasmic concentration of oxidized glutathione (GSSG) was significantly lower in the NAC group than in the 5% glucose group. Mitochondrial GSSG
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/GSH value, which is a marker of mitochondrial oxidative stress, was lower in the NAC group than in the 5% glucose group. Concentration of adenosine triphosphate in specimens of liver tissue was significantly higher in the NAC group than in the 5% glucose group. Neutrophils infiltrating to liver tissue was obtained using elutriator and neutrophil oxidative stress was measured with flow cytometric analysis. Neutrophil oxidative stress was lower in the NAC group than in the 5% glucose group.
In conclusion, NAC significantly reduced hepatocellular injury and hepatic oxidative stress in the animals with obstructive jaundice complicating endotoxin shock.
The effects of NAC on hepatic hemodynamics were investigated in dogs with obstructive jaundice complicating endotoxin shock. In dogs with obstructive jaundice and endotoxicemia, portal flow volume and hepatic microcirculatory tissue flow were reduced as compared with normal dogs. NAC significantly increased portal flow volume and hepatic microcirculatory tissue flow volume. Therefore, NAC can improve hepatic hemodynamics in dogs with obstructive jaundice complicating endotoxicemia. Less
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[Publications] Kaneshiro Y,Nakano H,Kumada K,Kitamura N,Shimura H,Kikawa G,Tatsuno M,Fujiwara Y,Baek Y,Sasaki J,Nagasaki H,Yamaguchi M.: "Augmentation of mitochondrial glutathione by S-adenosyl-L-methionine in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine deficient diet." Eur Surg Res. 30. 34-42 (1998)
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