LIVER & HEPATIC SYSTEM

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 - Test Sheet

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 →