2005 Fiscal Year Final Research Report Summary
Effects of Chronic Ethanol Administration on Disposition of Ethanol and its Metabolites and Drug-interaction
| Project/Area Number |
16590540
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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 |
Legal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
FUJIMIYA Tatsuya Yamaguchi University, Faculty of Medicine, Professor, 医学部, 教授 (50219044)
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| Co-Investigator(Kenkyū-buntansha) |
LIU Jinyao Yamaguchi University, Faculty of Medicine, Research Associate, 医学部, 助手 (60379956)
SHIMAMOTO Akiko Yamaguchi University, Faculty of Medicine, Research Associate, 医学部, 助手 (10379943)
KOZAWA Shuji Yamaguchi University, Faculty of Medicine, Research Associate, 医学部, 助手 (20379944)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Alcohol / Acetaldehyde / Acetate / Chronic alcohol intoxication / Pharmacokinetics / Alcohol Metabolism / Toxicokinetics / Ethanol |
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| Research Abstract |
Acetaldehyde and acetate (AcT) are the first and second metabolites of ethanol and detected in the plasma. Acetaldehyde and acetate redistribution from hepatic to peripheral tissues was reported during ethanol metabolism. Chronic ethanol administration affects ethanol metabolism. However, the effects of chronic ethanol intoxication on the disposition of its metabolites were hardly examined. In this study, we conducted the pharmacokinetic studies on the effects on its metabolites. Seven - weeks old, male Wister rats fed a nutritionally adequate liquid-diet in which ethanol was provided by 21% (3g/dl) or 35% (5g/dl) of the total calories. These diets were originally formulated by Lieber and DeCarli. At the beginning of the study, all rats were given the control liquid-diet for 4 days. For the next 4 days, the rats were fed either the control liquid-diet or 3g/dl ethanol liquid-diet. The 3g/dl group received this ethanol concentration for 45 days, while the 5g/dl group received a diet containing 4g/dl of ethanol for the next 3 days, followed by 5g/dl diet for 42 days. To maintain a similar caloric intake among the groups, the groups were pair-fed. Liquid-diet consumption was adjusted daily according to the animal's body weight and the daily liquid-diet intake. A bolus of EtOH saline solution (0.5,1.0,2.0 g/kg) was injected intravenously. Blood EtOH and AcT concentrations were measured by using head-space gas chromatography. The elimination rate of ethanol and the steady-state concentration of acetate increased with chronic ethanol exposure.
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