| Project/Area Number |
01480230
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | The Jikei University School of Medicine. |
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Principal Investigator |
FUJISAWA Kiyoshi The Jikei Univ. Sch. of Med. 1st Dept. of Int. Med. : Professor., 第一内科, 教授 (80056473)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAKAWA Junnichi The Jikei Univ. Sch. of Med. 1st Dept. of Int. Med. : Assistant., 第一内科, 助手 (00231548)
NAKAJIMA Hisato The Jikei Univ. Sch. of Med. 1st Dept. of Int. Med. : Assistant., 第一内科, 助手 (90207788)
NAKAHARA Masao The Jikei Univ. Sch. of Med. 1st Dept. of Int. Med. : Assistant., 第一内科, 助手 (30201669)
YAMAUCHI Masayoshi The Jikei Univ. Sch. of Med. 1st Dept. of Int. Med. : Assistant Professor., 第一内科, 構師 (20138811)
北原 敏久 東京慈恵会医科大学, 第一内科, 講師 (00119786)
小倉 和雄 東京慈恵会医科大学, 第一内科, 講師 (20119770)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Alcohol / Alcoholic liver disease / Vegetable oil / Animal oil / Leukotriene / P450 / Lipid peroxidation / 脂質過酸化 / 食事脂肪 / 不飽和脂肪酸 / 飽和脂肪酸 |
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| Research Abstract |
The amount and type of dietary fat is thought to be important in the pathogenesis of alcoholic liver disease according to our studies on the nutritional background of the American and Japanese patients with alcoholic liver disease. We investigated the role of amount and type of fat in the development of alcoholic liver disease.
1. Male Wistar rats were paired fed isocalorically with standard diet, low protein diet, low protein-high fat diet with or without 36 Cal% of ethanol. Hepatic collagen-bound hydroxyproline and triglyceride were higher in the low protein-ethanol group and the low protein-high fat-ethanol group than in the standard-ethanol group. Furthermore, hepatic collagen-bound hydroxyproline and trialyceride were much higher in the low protein-high fat-ethanol group compared to the low protein-ethanol group. Marked central fibrosclerosis was evident in the low protein-ethanol group and especially in the low protein-high fat-ethanol group accompanied with centrolobular fatty ch
… More
ange. Plasma level of acetate was the highest in the low protein-high fat-ethanol group.
2. The influence of acetate, as the metabolic product of ethanol and fats in the liver, on the occurrence and progression of alcoholic liver injury was studied. Male Sprague-Dawley rats were paired fed isocalorically with standard diet, acetate diet (containing 0.1 -mol sodium acetate), and with or without 46 Cal% of ethanol. Ethanol elimination rate was lower in the acetate-'ethanol group compared to the acetate group and the standard-ethanol group. Fatty and fibrotic changes in the liver were most prominent biochemically and histopathologically in the acetate-alcohol group. these data suggested that the effect of acetate may be an important factor in the development of alcoholic liver disease.
3. Male Sprague-Dawley rats were paired fed isocalorically with beef or safflower oil with or without 46 Cal% of ethanol for 12 weeks. We measured hepatic leukotrienes, hepatic lipid peroxide, fatty acid composition of liver, hepatic P450 activity, hepatic collagen-bound hydroxyproline and fibrogenic activity. Hepatic levels of lipid peroxide, linoleic acid, arachidonic acid and hydroxyproline iiere the highest in the safflox%rer-ethanol group. Fibrogenic activity and P450 activity were increased more significantly compared to those in the other paied groups. A significant positive correlation Y, 7as observed between hepatic level of leukotrienes and hepatic arachidonic acid or linoleic acid. A sigificant correlation was also found betx, ; een hepatic levels of lipid peroxide and arachidonic acid or linoleic acid.
In conclusion, vegitable oil containing more lineleic acid facilitates development of alcoholic liver disease. We postulate that accelerated generation of leukotrienes derived from arachidonate may be an important factor in the development of lipid peroxidation and liver disease in the allcoholic liver. Less
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