ANIT-Induced Cholestasis and Jaundice Model

Model Description

Alpha-naphthylisothiocyanate (ANIT), a hepatotoxic compound, induces intrahepatic cholestasis by targeting bile duct epithelial cells. Our model replicates human cholestatic liver injury through:

• Bile duct hyperplasia: Ductular reaction (CK19+ cell proliferation)
• Periductal inflammation: Neutrophil infiltration (MPO+ cells)
• Hepatocellular damage: Focal necrosis with elevated serum bilirubin (>2.5 mg/dL)

 Clinical Relevance:

✓ Mirrors human cholestasis: Alkaline phosphatase (ALP) elevation >3x ULN

✓ Drug-responsive pathology: Validated with ursodeoxycholic acid (UDCA) intervention

Applications

• Anti-cholestatic drug evaluation (FXR agonists, ASBT inhibitors)

• Bile acid metabolism studies

• Hepatobiliary toxicity screening

• Cholangiocyte-targeted therapy development

Modeling Protocol —— ANIT Induction Workflow

1. Group Design:

• Control Group: Vehicle (corn oil)
• Model Group: ANIT 100 mg/kg (oral gavage)
• Treatment Group: ANIT + test compound

2. Procedure:

• Day 1: ANIT administration (fasted state)
• Day 3: Terminal blood collection (retro-orbital) & necropsy

3.Key Parameters:

• Fasting protocol: 12h pre-dose to enhance ANIT bioavailability
• Humane endpoints: Serum total bilirubin >5 mg/dL ∙ Weight loss >15%

Validation & Testing