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LIVER & HEPATIC SYSTEM

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
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
NASH model Intracellular lipid accumulation	↓ NASH Model - Test Sheet	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 →

LIVER & HEPATIC SYSTEM

Porsolt

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