Carbon Tetrachloride (CCl4)-induced Model

Our suite of well-established metabolic disease models can help you evaluate key mechanistic questions

A well-established and widely accepted experimental mouse model to study liver fibrosis and cirrhosis is via Carbon tetrachloride (CCl4) injection. In many aspects, CCl4-induced hepatic fibrosis and cirrhosis in murine models mirrors the pattern of toxic damage seen with human disease, such as presence of stellate cell activation, macrophage infiltration, and alterations in matrix components including collagen-1, matrix metalloproteinases (MMPs) and their inhibitors. CCl4 injection elicits a reproducible and predictable fibrotic and cirrhotic response in the liver, making it a valuable preclinical resource for pharmacological and pathophysiological studies.

NASH (Non-alcoholic Steatohepatitis) Mouse Model

Increased liver damage in CCl4-induced NASH mice. (A) Experimental timeline for CCl4 induction of Non-alcoholic Steatohepatitis (NASH), 6-8-week-old male C57BL/6 mice were injected intraperitoneally with CCl4 at the following concentrations: 0.25, 0.5 and 0.75 mL/kg twice a week. Blood biochemical and histological staining was performed at 4 weeks, 6 weeks and 8 weeks after induction. (B) Mouse body weight and (C) liver weight to body weight ratio at 6 and 8 weeks of induction were measured. (D, E) Serum ALT and AST levels were measured. The results indicate that liver weight, ALT and AST levels were significantly increased in CCl4-induced NASH mice compared to control mice. Values are represented as mean ± SEM, n = 5.

Analysis of Liver Cells in NASH Mice

(A) H&E staining of liver tissue sections was performed at 4 weeks, 6 weeks and 8 weeks after induction with different concentrations (0.25 mL/kg, 0.5 mL/kg, 0.75 mL/kg) of CCl4. Representative sections are shown here (n=5). (B) Sirius red staining. Results indicated that H&E staining of liver tissue sections showed extensive hepatocyte steatosis, ballooning degeneration and intralobular inflammation after CCl4 induction. CCl4 also induced significant liver fibrosis and increased liver fibroblasts compared to the control group. These results indicate that CCl4 can successfully establish a NASH mouse model. Values are represented as mean ± SEM, n = 5.

Assessment of Liver Fibrosis in NASH Mice

Liver tissue sections were prepared 4 weeks, 6 weeks and 8 weeks after induction with different concentrations (0.25 mL/kg, 0.5 mL/kg, 0.75 mL/kg) of CCl4. (A, B) Immunohistochemistry showed significantly increased fibroblast marker α-SMA in the liver. Values are expressed as mean ± SEM. ***p<0.001, ****p<0.0001.

OCA Efficacy Validation for Liver Fibrosis Mouse Models

(A) Representative pictures of Sirius red staining showing liver fibrosis after 3 weeks of CCl4 induction and obeticholic acid (OCA) treatment.  (B) Statistic data of Sirius red  staining. Values are expressed as mean ± SEM. *p<0.05.

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