“From running the experiments myself to designing them to be run by others, the initial steps have always been my favourite. Those moments when a sponsor explains the challenge he/she/they are facing, and together we brainstorm to assemble a solution. Eventually, a ground-breaking idea—a parameter, a test, something—comes to mind, which crystallizes the solution. At that point, we both know that this idea changes everything: it collapses obstacles and opens the path forward. That moment has remained one of my greatest motivators throughout the years.”
Dan’s undergrad studies in Biochemistry (Bishop’s University) were followed by graduate studies in Thoracic Physiology (Université de Sherbrooke). Dan’s post-graduate work was in Cardiovascular Pharmacology and Cardiology.
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MCDD-induced Liver Fibrosis
Purpose
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.
Method
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.
Study outcome
- 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
Compliance
Non-GLP compliant. The study is best suited to demonstrate efficacy in discovery-phase preclinical development strategies.
Dany Salvail
Ph.D., Vice-President.
