Effects of central amino acid metabolism on hepatic encephalopathy
| Project/Area Number |
13671589
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Ehime University |
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Principal Investigator |
ADACHI Naoto Ehime University, Faculty of Medicine University Hospital, Assistant Professor, 医学部附属病院, 講師 (50253315)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Tatsuru Ehime University, Faculty, of Medicine, Professor, 医学部, 教授 (50033436)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Hepatic encephalopathy / Monoamines / Dopamine / Amino acids / Glutamate / Flumazenil / Microdialysis / Rats / セロトニン |
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| Research Abstract |
Several reports attested alleviation of hepatic encephalopathy by flumazenil, an antagonist of benzodiazepine receptors. Because benzodiazepine receptor activation causes changes in the central monoaminergic activity, which are involved in the mechanism for hepatic encephalopathy, effects of flumazenil on the central monoaminergic activity were evaluated in acute hepatic failure produced by ischemia-reperfusion injury in rats. Liver ischemia was provoked by 90-min occlusion of the left portal vein. Flumazenil was administered three times, 0, 6, and 24 h after reperfusion (1 mg/kg, i.p., each), and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines and their metabolites were evaluated in the striatum with a microdialysis procedure. The extracellular concentration of 3, 4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 39% of that in sham-operated animals 24 h after surgery, although the dopamine level did not change. The treatment with flumazenil completely abolished the decrease in the metabolite. There were no remarkable differences in the levels of serotonin and its metabolite. Although the glutamate level in injured animals decreased to 42% of that in sham-operated animals, no remarkable increase in the glutamate level was observed in animals treated with flumazenil. Spontaneous motor activity was decreased 24 h after surgery in animals subjected to liver ischemia, and the activity was recovered by flumazenil administration. The improvement of dopaminergic activity may be a contributing factor in the alleviation of hepatic encephalopathy by flumazenil.
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Report
(3 results)
Research Products
(6 results)
