Carbon Tetrachloride (CCl₄)-Induced Rodent Hepatic Injury Model

The availability of appropriate experimental animal models is of prime importance to provide a better understanding of the pathogenesis of liver diseases and allow the development and evaluation of new therapeutic interventions. Carbon tetrachloride (CCl₄) is a well-known hepatotoxic agent frequently used to induce both acute and chronic liver injury in a wide range of laboratory animals. Particularly, Creative Biolabs provides CCl₄-induced hepatic injury model and a variety of administration routes and clinically relevant endpoints for the development of protective drugs.

Introduction of Liver Diseases

The liver is the major organ to metabolize and detoxify metabolites and xenobiotics. However, these metabolic reactions can potentially lead to liver injury. With the speeding up of the rhythm of lifestyles and changing diets in recent years, the risk of liver disease has been increasing greatly. Currently, acute liver failure and chronic liver disease (e.g., steatosis and fibrosis) have become challenging problems worldwide in medical practices. Despite considerable and continuous efforts, an effective treatment against these diseases resulting in fewer side effects is still lacking.

The Mechanisms of CCl₄-Induced Liver Injury

CCl₄ is an acknowledged hepatotoxin capable of causing acute or chronic liver injury characterized by centrilobular necrosis, inflammatory cell infiltration, centrilobular fatty changes, and apoptosis. If the damage outpaces the repair capacity of the liver, it will eventually develop into fibrosis and cirrhosis and even hepatocellular carcinoma (HCC). Consequently, a single dose of CCl₄ will lead to centrizonal necrosis and steatosis, while the prolonged administration will cause liver fibrosis, cirrhosis, and HCC.

CCl₄ impairs hepatocytes via alteration of the permeability of the plasma membrane and membranes of cell organelles. Moreover, it can be converted to highly reactive free radical metabolites by the cytochrome P450 in the liver, which in turn reduce antioxidant enzymes activity and eventually lead to membrane lipid peroxidation. As a result, it has become an extensively used model to assess the hepatoprotective effects and antioxidative properties of new therapeutics.

Carbon Tetrachloride (CCl4)-Induced Rodent Hepatic Injury Model Fig.1 Liver specimen from the control group (a) and CCl₄ challenged animals (b) stained with Sirius Red. (Scholten et al. 2015)

Our Capabilities

Creative Biolabs is capable of offering CCl₄-induced acute or chronic liver injuries models in both rats and mice. Blood and liver tissue samples can be collected for subsequent biochemical analysis and histopathological analysis. Our preclinical center offers a broad spectrum of assessments to evaluate the hepatoprotective and antioxidative effects of potential drugs, including but not limited to:

Blood/tissue collections
Biochemical analysis (e.g. alanine aminotransferase, aspartate aminotransferase, glutathione S-transferase)
Lipid peroxidation (e.g. liver malondialdehyde (MDA) assay)
Histopathological examination (e.g. hematoxylin & eosin (H&E), Masson's trichrome and Sirius red)
Immunohistochemistry
Biomarker measurement (e.g. enzyme-linked immunosorbent assay (ELISA), quantitative PCR and western blot)