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Modeling liver fibrosis in rodents

Modeling liver fibrosis in rodents
Modeling liver fibrosis in rodents
Animal models of hepatic fibrosis provide a means to study the cell and molecular mediators of fibrosis in a serial manner during both progression and recovery.
Several approaches to induction of fibrosis have been described. Of these, CCl4 intoxication in rats and mice is probably the most widely studied. In addition, the CCl4 model is the best characterized with respect to histological, biochemical, cell, and molecular changes associated with the development of fibrosis. CCl4 can be given intraperitoneally or by oral gavage; it induces zone III necrosis and hepatocyte apoptosis with associated hepatic stellate cell activation and tissue fibrosis. With repetitive dosing CCl4 can be used to induce bridging hepatic fibrosis (4 wk of twice-weekly dosing), cirrhosis (8 wk of twice-weekly dosing) and advanced micronodular cirrhosis (12 wk of twice-weekly dosing). In addition, for each of these models spontaneous recovery from fibrosis can be studied after cessation of dosing. Mechanistic studies using gene knockout and transgenic animals can also be established using CCl4. Together these models have provided unparalleled insights into the mechanisms underlying hepatic fibrosis.
liver fibrosis, CCl4, rodents, hepatic stellate cell, collagen
1543-1894
237-250
Constandinou, Christothea
76b26759-3ed1-43b8-a462-acc79299e102
Henderson, Neil
1a283a67-c5f7-48f5-8a7a-dbb023e03708
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2
Constandinou, Christothea
76b26759-3ed1-43b8-a462-acc79299e102
Henderson, Neil
1a283a67-c5f7-48f5-8a7a-dbb023e03708
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2

Constandinou, Christothea, Henderson, Neil and Iredale, John P. (2005) Modeling liver fibrosis in rodents. Methods in Molecular Medicine, 117, 237-250.

Record type: Article

Abstract

Animal models of hepatic fibrosis provide a means to study the cell and molecular mediators of fibrosis in a serial manner during both progression and recovery.
Several approaches to induction of fibrosis have been described. Of these, CCl4 intoxication in rats and mice is probably the most widely studied. In addition, the CCl4 model is the best characterized with respect to histological, biochemical, cell, and molecular changes associated with the development of fibrosis. CCl4 can be given intraperitoneally or by oral gavage; it induces zone III necrosis and hepatocyte apoptosis with associated hepatic stellate cell activation and tissue fibrosis. With repetitive dosing CCl4 can be used to induce bridging hepatic fibrosis (4 wk of twice-weekly dosing), cirrhosis (8 wk of twice-weekly dosing) and advanced micronodular cirrhosis (12 wk of twice-weekly dosing). In addition, for each of these models spontaneous recovery from fibrosis can be studied after cessation of dosing. Mechanistic studies using gene knockout and transgenic animals can also be established using CCl4. Together these models have provided unparalleled insights into the mechanisms underlying hepatic fibrosis.

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More information

Published date: 2005
Keywords: liver fibrosis, CCl4, rodents, hepatic stellate cell, collagen

Identifiers

Local EPrints ID: 27001
URI: http://eprints.soton.ac.uk/id/eprint/27001
ISSN: 1543-1894
PURE UUID: 564b105d-419f-4c5f-8195-eebfb34feeb0

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 27 Apr 2022 07:34

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Contributors

Author: Christothea Constandinou
Author: Neil Henderson
Author: John P. Iredale

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