Porsolt's experience in preclinical safety and efficacy has led to the development of models that focus on the liver and hepatic system. This is an important part of the development process to better understand the effects of compounds on the liver and hepatic system.
IN VITRO MODELS
Starting with a core expertise in polarized primary cultures of rat hepatocytes, Porsolt set up a tool box to support drug discovery in hepatology.
From cell-based screening up to biomarker studies in liver tissues, we offer quantitative and automated approaches to characterize the effects of drug candidates on liver functions and explore their mechanism of action (MOA).
Primary cultures of rat and human hepatocytes
• in vivo-like features: drug metabolizing-enzymes, polarized phenotype, bile canaliculi networks
Polarized fresh primary rat hepatocytes form bile canaliculi networks, thus mimicking in vivo liver organization →
• in vitro liver disease models based pharmacological treatment
• Screening format: microplates
>>> High-biological relevance, fast turnaround
High Content Analysis
FUNCTIONAL ASSAYS |
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LDL uptake |
HepG2 cell line |
PF 3.10 |
Cholestasis / Bile canaliculi network |
Primary hepatocytes - sandwich configuration |
PF 3.16 |
Acetaminophen toxicity model (GSH contents, cytolysis) |
Mouse primary hepatocytes |
PF 3.41 |
Steatosis/Lipid, intracellular accumulation: neutral lipids |
Multiple cellular models |
PF 3.29 |
NASH model Intracellular lipid accumulation |
Primary Human and primary mouse hepatocytes |
PF 6.1 |
Lipid, intracellular accumulation: phospholipids |
Multiple cellular models |
PF 3.30 |
Mitochondrial Membrane Potential |
Multiple cellular models |
PF 3.3 |
NAD(P)H / FAD |
Multiple cellular models |
PF 3.31 |
CELL SIGNALING ASSAYS | ||
Glutathione (GSH), intracellular GSH content |
Multiple cellular models |
PF 3.28 |
Acetaminophen toxicity model (GSH contents, cytolysis) |
Mouse primary hepatocytes |
PF 3.41 |
Cytolysis |
Multiple cellular models |
PF 3.4 |
Heme Oxygenase 1 expression |
Multiple cellular models |
PF 3.25 |
NQO1 expression |
Multiple cellular models |
PF 3.24 |
High Content Histology
• Generation of in vivo models of liver pathologies
• High-content analysis of liver tissue microarrays
• Automated and multiplexed biomarker quantification
MRP2 expression |
Primary hepatocytes - sandwich configuration - hepatic tissue |
PF 3.5 |
Immunostaining of the transporter MRP2 (red) in rat liver tissue. Nuclei are stained in blue. MPRP2 localization highlights bile canaliculi network and hepatobiliary function.
IN VIVO MODELS
Carbon tetrachloride (CCl4) (acute model) | Rat | LI 1 |
Acetaminophen (acute model) | Mouse | LI 2 |
Bile Duct Ligation (BDL) (chronic model) | Rat | CV 2.7 |
NEW! Non-alcoholic steatohepatitis (NASH) model |
Mouse – Rat | In development |
Focus on Carbon tetrachloride (CCl4) acute model in rats:
Carbon tetrachloride (CCl4) is an hepatic toxin widely used for experimental induction of liver injury and oxidative stress.
Effect of CCl4 on Alanine Amino Transferase (ALAT) and Aspartate Amino Transferase (ASAT) levels →