MCDD-induced Liver Fibrosis

Effect of test article on Methionine and Choline Deficient Diet (MCDD)-induced Liver Fibrosis

Request a Study Outline from IPST

Overview

Liver fibrosis represents a classical outcome of many chronic liver diseases irrespectively of the etiology of injury. It results from successive rounds or chronic activation of the physiological wound-healing response that sustains persistent fibrogenesis and leads to progressive fibrosis of the organ through inflammation or reactive oxygen species mechanism.

Compliance

Non-GLP compliant. The study is best suited to demonstrate efficacy in discovery-phase preclinical development strategies.

Purpose of the Study

The MCD diet is one of the most commonly used animal models of NASH, as it induces a liver pathology that recapitulates the sequence and progression of liver pathology seen in humans. In addition, choline deficiency impairs hepatic VLDL secretion. Thus, lipid is deposited into the liver. Furthermore, oxidative stress and changes in cytokines and adipocytokines occur, contributing to the liver injury. We normally induce NASH with fibrosis after 8 to 12 weeks on MCD diet. The aim of this study will be to demonstrate the efficacy of test article during prophylaxis or therapeutic intervention.

Parameters Monitored

  • Plasmatic liver inflammation biomarkers (ALP, ALT, ASP, bilirubin)
  • Liver oxidative stress marker (MDA, lipid peroxidation)
  • Liver inflammation marker (TNF-alpha)
  • Histopathology of formalin-fixed and paraffin-embedded liver section
    • H&E staining for morphology and steatosis
    • Masson’s trichrome for fibrosis
    • Sirius red for collagen content

Study Timeline

  • One week to finalize the protocol/formulation
  • In vivo disease development phase: 8 to 12 weeks
  • Terminal surgery and acquisition: 1 day of surgery per experimental group
  • Analysis of biomarkers parameters: 7 days
  • Morphometric and histopathological examination: 14 days following reception of the slides

Reporting

Non-audited report 2 weeks following the last functional measurement.