CCl₄ Liver Fibrosis Rodent Model

CCl4-Induced Liver Fibrosis Rodent Model for Preclinical Efficacy Studies

Carbon tetrachloride (CCl4) exposure induces reproducible hepatocellular injury, inflammation, and progressive liver fibrosis in rodents. The model is widely used to evaluate therapeutic candidates targeting hepatic injury, fibrogenesis, extracellular matrix deposition, inflammation, and fibrosis resolution.

At IPST, the CCl4-induced liver fibrosis model can be used to assess anti-fibrotic and hepatoprotective drug candidates using integrated biochemical, histological, and morphometric endpoints. The study design can be adapted to the sponsor’s therapeutic strategy, including prevention, intervention, or reversal-oriented protocols.

CCl4-Induced Liver Fibrosis - Methodology

Species: mice, rats
Induction: repeated intraperitoneal administration of carbon tetrachloride
Typical dosing frequency: twice weekly
Typical in-life phase: approximately 4 weeks
Typical total study duration: approximately 7 weeks, depending on treatment schedule and endpoint requirements
Disease features induced: hepatocellular injury, inflammation, collagen deposition, and liver fibrosis
Study design: preventive, therapeutic, or reversal-style treatment windows can be implemented depending on the mechanism of action

Repeated CCl4 exposure produces liver injury followed by activation of fibrogenic pathways and extracellular matrix accumulation.

This model is particularly useful for evaluating compounds intended to reduce liver damage, limit fibrotic progression, decrease collagen deposition, modulate inflammatory responses, or promote fibrosis regression.

CCl4-Induced Liver Fibrosis - Readouts & Application

Readouts:

Blood chemistry: ALT, AST, bilirubin, and additional liver injury markers as required
Liver weight and liver index
Histology: H&E and Picrosirius Red staining
Fibrosis scoring: semi-quantitative scoring, including Ishak or study-specific scoring systems
Collagen quantification: collagen area, fibrosis burden, and morphometric analysis
Inflammation and tissue injury: necrosis, inflammatory infiltrates, hepatocellular degeneration, and architectural disruption
Biomarkers: tissue or circulating biomarkers can be added based on the therapeutic mechanism

Application:

The CCl4-induced liver fibrosis model is a well-established platform for evaluating anti-fibrotic, anti-inflammatory, and hepatoprotective therapeutic candidates. It is particularly useful when biochemical evidence of liver injury must be integrated with histological and morphometric assessment of fibrosis.

At IPST, the model can support efficacy studies designed to assess reductions in liver injury, collagen deposition, fibrosis severity, inflammatory burden, and overall hepatic tissue remodeling. Endpoint packages can be tailored to the sponsor’s therapeutic hypothesis and development stage.