A novel model of CCl4-induced cirrhosis with ascites in the mouse.
Journal of Hepatology. 2009-12-01; 51(6): 991-999
DOI: 10.1016/j.jhep.2009.09.008
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Domenicali M(1), Caraceni P, Giannone F, Baldassarre M, Lucchetti G, Quarta C,
Patti C, Catani L, Nanni C, Lemoli RM, Bernardi M.
Author information:
(1)Department of Clinical Medicine, Alma Mater Studiorum University of Bologna,
Azienda Ospedaliera-Universitaria Policlinico S. Orsola-Malpighi, Via Massarenti
9, 40138 Bologna, Italy.
BACKGROUND/AIMS: The current approaches to study the molecular mechanisms
involved in the pathophysiology of liver diseases often rely on the use of
transgenic mice. However, experimental models of decompensated cirrhosis have not
been clearly established in mice. Thus, we aimed to set an efficient and
well-tolerated protocol to induce cirrhosis in mice able to progress up to the
ascitic stage.
METHODS: C57BL/6N mice received CCl(4) subcutaneously, intraperitoneally or by
inhalation. In the latter group, gaseous CCl(4) was administered according to
three different schedules: increasing exposure times, twice weekly (traditional
protocol; TP), short inhalation cycles, twice or three times weekly.
RESULTS: Portal hypertension, sodium retention, and ascites developed in all
groups between 11 and 15 weeks. Mortality reached 70% in the TP group, but it was
only 0-10% with all other protocols. All the inhalation groups had significantly
more ascites at sacrifice than those receiving CCl(4) subcutaneously and
intraperitoneally. Extensive abdominal adhesions and evidence of enhanced hepatic
inflammation, as suggested by the increased gene expression of pro-inflammatory
cytokines in liver tissue, were found in the intraperitoneal group, while large
granulomas at the injection site and marked neutrophil infiltration of lungs
developed in the subcutaneous group. No extra-hepatic damage could be detected in
mice inhaling CCl(4).
CONCLUSIONS: The use of short cycles of CCl(4) inhalation represents a novel,
safe, and effective method to induce decompensated cirrhosis in mice.
Intraperitoneal CCl(4) leads instead to abdominal adhesions precluding a correct
evaluation of ascites, while subcutaneous CCl(4) causes an unwanted systemic
inflammatory response.
DOI: 10.1016/j.jhep.2009.09.008
PMID: 19853952 [Indexed for MEDLINE]