DOI: 10.1002/hep.1840060503. Ethanol-induced liver fibrosis in rats fed high fat diet

Ethanol-induced liver fibrosis in rats fed high fat diet

10.1002/hep.1840060503

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Hepatology (276)

Abstract

Severe hepatic steatosis and focal necrosis of hepatocytes have previously been induced in rats by continuous intragastric infusion of ethanol and a diet containing only 5% fat as a per cent of total calories as reported by us previously. Since the ethanol diet fed ad libitum with such a low level of fat has previously failed to produce alcoholic fatty liver, continuously high blood alcohol levels achieved in this model appeared to be key in induction of the progressive pathologic lesions in the liver. In the current study, effects of increased fat intake on alcohol-induced liver injury were investigated. Seventeen pairs of male Wistar rats were implanted with gastrostomy cannulas and infused with a liquid diet containing 25% of total calories as fat plus ethanol or isocaloric dextrose. Ethanol intake was progressively increased from 32% up to 47% of total calories to maintain sustained intoxication for 30 to 120 days. Light and electron microscopic examination of the liver revealed moderate to severe fatty infiltration in all of the ethanolfed rats, of which 14 had spotty or zonal necrosis in the centrilobular areas accompanied by polymorphonuclear and mononuclear cell infiltration. In addition, fibrosis was observed in association with the necrotic lesions or with large-droplet steatosis. Reticulin and trichrome stains clearly demonstrated fine fibrosis, including perivenular fibrosis as well as septum formation progressing to bridging fibrosis. Furthermore, increased numbers of Ito cells and myofibroblasts were observed in the perivenular fibrotic areas. These results demonstrate striking potentiation of alcohol-induced liver injury by the increased fat intake or by the concomitant decrease in carbohydrate intake. This model, which represents the first rat model to achieve such advanced experimental alcohol-induced liver injury, possesses the obvious potential for further use in studies of ethanol-nutrient interactions in the pathogenesis of alcohol-induced liver injury.

Bibliography

Tsukamoto, H., Towner, S. J., Clofalo, L. M., & French, S. W. (1986). Ethanol-induced liver fibrosis in rats fed high fat diet. Hepatology, 6(5), 814â822.

Authors 4

Hidekazu Tsukamoto (first)
Sally J. Towner (additional)
Lefran M. Clofalo (additional)
Samuel W. French (additional)

References 35 Referenced 232

10.1073/pnas.72.2.437 / Proc Natl Acad Sci USA by Lieber (1975)
10.1056/NEJM197401172900303 / N Engl J Med by Rubin (1974)
10.1093/ajcn/23.9.1151 / Am J Clin Nutr by Barboriak (1970)
Animal models of alcoholism? In: , , eds. Animal models in alcohol research. New York: Academic Press, 1980: 99–117. / Animal models in alcohol research by Cicero (1980)
10.1172/JCI105200 / J Clin Invest by Lieber (1965)
10.1111/j.1530-0277.1982.tb05017.x / Alcoholism Clin Exp Res by Lieber (1982)
10.1016/S0016-5085(82)80389-2 / Gastroenterology by Singh (1982)
{'key': '10.1002/hep.1840060503-BIB8', 'first-page': '97', 'volume': '1', 'author': 'Rao', 'year': '1985', 'journal-title': 'Biochem Arch'} / Biochem Arch by Rao (1985)
{'key': '10.1002/hep.1840060503-BIB9', 'first-page': '1449', 'volume': '26', 'author': 'Porta', 'year': '1967', 'journal-title': 'Fed Proc'} / Fed Proc by Porta (1967)
10.1093/ajcn/33.2.221 / Am J Clin Nutr by Frank (1980)
10.1002/hep.1840050212 / Hepatology by Tsukamoto (1985)
10.1111/j.1530-0277.1985.tb05046.x / Alcoholism Clin Exp Res by Tsukamoto (1985)
{'key': '10.1002/hep.1840060503-BIB13', 'first-page': 'r595', 'volume': '247', 'author': 'Tsukamoto', 'year': '1984', 'journal-title': 'Am J Physiol'} / Am J Physiol by Tsukamoto (1984)
, , et al. An improved animal model for production of alcoholic liver damage using nutritionally adequate liquid diet containing ethanol and 4-methylpyrazole. In: , , eds. Animal models in alcohol research. New York: Academic Press, 1982; 445–452. / Animal models in alcohol research by Lindros (1982)
10.1093/jn/33.2.155 / J Nutr by Salmon (1947)
10.1084/jem.100.6.605 / J Exp Med by Klatskin (1954)
10.1093/ajcn/26.11.1234 / Am J Clin Nutr by Barak (1973)
10.1016/S0271-5317(84)80145-1 / Nutr Res by Rao (1984)
10.1016/S0022-2275(20)37328-4 / J Lipid Res by Lokesh (1981)
{'key': '10.1002/hep.1840060503-BIB20', 'first-page': '417', 'volume': '98', 'author': 'Shaw', 'year': '1981', 'journal-title': 'J Lab Clin Med'} / J Lab Clin Med by Shaw (1981)
10.1002/hep.1840040521 / Hepatology by French (1984)
10.1073/pnas.72.3.1137 / Proc Natl Acad Sci USA by Israel (1975)
10.1073/pnas.79.17.5415 / Proc Natl Acad Sci USA by Ji (1982)
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, , et al. Hypermetabolic state: oxygen availability and alcohol induced liver damage. In: , eds. Biochemistry and pharmacology of ethanol. New York: Plenum, 1979; 443. / Biochemistry and pharmacology of ethanol by Israel (1979)
10.1016/0002-9343(81)90124-8 / Am J Med by Taasam (1981)
{'key': '10.1002/hep.1840060503-BIB27', 'first-page': '2472', 'volume': '41', 'author': 'Israel', 'year': '1982', 'journal-title': 'Fed Proc'} / Fed Proc by Israel (1982)
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10.1016/S0016-5085(85)80003-2 / Gastroenterology by Hayashi (1985)
{'key': '10.1002/hep.1840060503-BIB31', 'first-page': '695', 'volume': '98', 'author': 'Popper', 'year': '1980', 'journal-title': 'Am J Pathol'} / Am J Pathol by Popper (1980)
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{'key': '10.1002/hep.1840060503-BIB34', 'first-page': '459', 'volume': '107', 'author': 'Okanoue', 'year': '1983', 'journal-title': 'Arch Path Lab Med'} / Arch Path Lab Med by Okanoue (1983)
{'key': '10.1002/hep.1840060503-BIB35', 'first-page': '145', 'volume': '106', 'author': 'Nakano', 'year': '1982', 'journal-title': 'Am J Pathol'} / Am J Pathol by Nakano (1982)

Dates

Type	When
Created	18 years, 5 months ago (March 3, 2007, 2:53 p.m.)
Deposited	9 months ago (Dec. 1, 2024, 6:01 a.m.)
Indexed	1 week, 2 days ago (Aug. 23, 2025, 9:43 p.m.)
Issued	39 years ago (Sept. 1, 1986)
Published	39 years ago (Sept. 1, 1986)
Published Print	39 years ago (Sept. 1, 1986)

Funders 0

None

BibTeX

@article{Tsukamoto_1986, title={Ethanol-induced liver fibrosis in rats fed high fat diet}, volume={6}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.1840060503}, DOI={10.1002/hep.1840060503}, number={5}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Tsukamoto, Hidekazu and Towner, Sally J. and Clofalo, Lefran M. and French, Samuel W.}, year={1986}, month=sep, pages={814–822} }

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