Liver fibrosis is caused due to the accumulation of extracellular matrix (ECM), leading to the formation of fibrous scar tissue. This ECM buildup triggers inflammation, which drives the progression of fibrosis. If left untreated, liver fibrosis can progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC).
Aragen offers a diverse range of liver fibrosis in vivo models, each tailored to address different causes and stages of liver damage.
- Hepatotoxin-Induced Models (CCl4 and TAA): For studying chemically induced liver fibrosis, commonly used in hepatology research.
- Metabolic Dysfunction-Associated Steatohepatitis (MASH) Models (CDAHFD and Western Diet + CCl4): Simulate the effects of MASH, a major driver of liver fibrosis.
- Biliary Fibrosis Models (DDC and ANIT): For exploring fibrotic mechanisms in cholestatic liver diseases.
Hepatotoxin-Induced Models (CCl4 and TAA)
Carbon tetrachloride (CCl4) and thioacetamide (TAA) are commonly used hepatotoxins that induce liver injury and fibrosis by causing hepatocyte damage and subsequent activation of fibrogenic pathways. These models mimic chemically induced liver damage and are essential for understanding liver fibrosis progression, hepatocyte regeneration, and the fibrotic response. They are widely used to evaluate potential hepatoprotective and anti-fibrotic treatments in liver diseases.
Induction of liver fibrosis
CCL administration
Treatment
(options: IP, IV, SC, IM, ID, intranasal, sublingual)
Terminate study/harvest organs
Data analysis
(Body & Liver weights, Liver enzymes, Survival, Hydroxyproline, Histology)
Draft/final report
Induction of liver fibrosis
TAA administration
Treatment
(options: IP, IV, SC, IM, ID, intranasal, sublingual)
Terminate study/harvest organs
Data analysis
(Body & liver weights, Liver enzymes, Survival, Hydroxyproline, Histology)
Draft/final report
Metabolic Dysfunction-Associated Steatohepatitis Models: CDAHFD and Western Diet + CCl4
The Metabolic Dysfunction-Associated Steatohepatitis (MASH) models, such as CDAHFD (choline-deficient, amino acid-defined, high-fat diet) or Western diet combined with CCl4, simulate metabolic dysfunction-associated steatohepatitis (MASH), a major driver of liver fibrosis. These models are important for studying the pathogenesis of MASH, liver inflammation, and fibrosis associated with metabolic dysfunction. They also provide an effective platform for testing therapeutic approaches targeting MASH and its progression to cirrhosis.
Methodology
- Study animals: C57BL/6
- Disease induction: Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) consisting of 60 kcal% fat and 0.1% methionine by weight
- Option of test article administration: PO, IP, IV, IM, SC, nebulization, and osmotic pumps
- Treatment regimen: Therapeutic or Prophylactic
- References: Model adapted from Matsumoto et al., 2013 Int. J. Exp. Pathol.
Study Parameters
Methodology
Study Analysis
Biliary Fibrosis Models (DDC and ANIT)
Biliary fibrosis models, such as DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and ANIT (alpha-naphthyl isothiocyanate), are used to study cholestatic liver diseases by inducing liver injury through bile flow obstruction. These models replicate key features of cholestasis-induced fibrosis, including liver inflammation, bile duct proliferation, and fibrosis. DDC specifically causes bile duct obstruction, leading to inflammation, ductular proliferation, and fibrosis, making it a valuable tool for investigating liver injury mechanisms and evaluating therapies targeting bile acid metabolism and fibrosis in cholestatic conditions.
Induction of liver fibrosis
DDC Diet
Treatment
(options: IP, IV, SC, IM, ID, intranasal, sublingual)
Terminate study/harvest organs
(2-6 weeks post fibrosis induction)
Data analysis
(Body & liver weights, Liver enzymes, Survival, Hydroxyproline, histology)
Draft/final report
