Abstract: Liver fibrosis is a key process in the progression of chronic liver diseases. It occurs when liver cells experience repeated damage and regeneration, leading to an excessive build-up and abnormal distribution of extracellular matrix components, such as collagen, glycoproteins, and proteoglycans, in the liver.
In vivo models of hepatic fibrosis are crucial for studying the development of liver fibrosis and evaluating potential antifibrotic therapies. These models aim to replicate the progressive scarring of liver tissue that occurs in chronic liver diseases. In vivo hepatic fibrosis models can be classified based on their underlying causes, including chemical, dietary, surgical, transgenic, and immune-mediated models. For instance, carbon tetrachloride (CCI4) is known to induce significant fibrosis, while models of non-alcoholic steatohepatitis (NASH) are used to investigate advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Among various models, the carbon tetrachloride (CCI4) induced liver fibrosis model is one of the most widely used experimental approaches. Its popularity stems from its reliability, reproducibility, cost-effectiveness, ease of implementation, and resemblance to human fibrotic liver injury. While this model is considered the gold standard in fibrosis research, it has several limitations that researchers must carefully consider. For instance, an overdose of CCI4 can lead to substantial hepatocellular necrosis, particularly in the centrilobular area. This can cause acute liver failure, which may result in rapid death rather than fibrosis. This review aims to outline the optimal experimental parameters for the CCI4-induced liver fibrosis model. It covers aspects such as the appropriate doses of CCI4, routes of administration, duration, frequency, and the choice of vehicle needed to establish a pathologically relevant model of liver fibrosis in experimental animals. The review also seeks to investigate therapeutic effects and contribute to the development of new medications.