A novel model of CCl4-induced cirrhosis with ascites in the mouse

Marco Domenicali, Paolo Caraceni, Ferdinando Giannone, Maurizio Baldassarre, Giovanna Lucchetti, Carmelo Quarta, Corrado Patti, Lucia Catani, Cristina Nanni, Roberto M. Lemoli, Mauro Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

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 CCl4 subcutaneously, intraperitoneally or by inhalation. In the latter group, gaseous CCl4 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 CCl4 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 CCl4. Conclusions: The use of short cycles of CCl4 inhalation represents a novel, safe, and effective method to induce decompensated cirrhosis in mice. Intraperitoneal CCl4 leads instead to abdominal adhesions precluding a correct evaluation of ascites, while subcutaneous CCl4 causes an unwanted systemic inflammatory response.

Original languageEnglish
Pages (from-to)991-999
Number of pages9
JournalJournal of Hepatology
Volume51
Issue number6
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Ascites
  • Carbon tetrachloride
  • Experimental cirrhosis
  • Mice
  • Portal hypertension

ASJC Scopus subject areas

  • Hepatology

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