ΞMENU

HEPATOLOGY

Starting with a core expertise in polarized primary cultures of rat hepatocytes, Fluofarma set up a tool box to support 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 & HUMAN HEPATOCYTES

Polarized fresh primary rat hepatocytes form bile canaliculi networks, thus mimicking in vivo liver organization.

> in vivo-like features: drug metabolizing-enzymes, polarized phenotype, bile canaliculi networks

> in vitro liver disease models based pharmacological treatment

> Screening format: microplates

>>> High-biological relevance, fast turnaround

LIVE CONTENT IMAGING

Dose-dependent cytotoxic effects of arsenic trioxide on primary rat hepatocytes over 24 hours, by live-content imaging.

> No more hidden drug effects: kinetic quantification of drug effects on hepatocyte viability or bile canaliculi structure over several days.

> Accurate compound profiling: generation of time-dependent EC50 values.

>>> Phenotypic screening & drug profiling

HIGH CONTENT ANALYSIS

> Functional assays: Lipid accumulation, hepatobiliary function, redox state, LDL uptake, NADH/FAD content, intracellular Ca2+, mitochondrial function, ...

> Cell signaling assays: NQO1, HO1, MRP2, GSH, p53, caspase 3/7 ...

>>> High-content screening & mechanism of action studies

Identification of hepatoprotective compounds activating NRF2 signaling in primary cultures of rat hepatocytes
> Download the document

HIGH-CONTENT HISTOLOGY

Immunostaining of the transporter MRP2 (red) in rat liver tissue. Nuclei are stained in blue. MPRP2 localization highlights bile canaliculi network and hepatobiliary function.

> Generation of in vivo models of liver pathologies

> High-content analysis of liver tissue microarrays

> Automated and multiplexed biomarker quantification

>>> In vivo proof of drug efficacy / safety / mechanism of action

HEPATOLOGY READOUTS

LDL uptake	HepG2 cell line	PF 3.10
Cholestasis / Bile canaliculi network	Primary hepatocytes - sandwich configuration - hepatic tissue	PF 3.16
Glutathione (GSH), intracellular GSH content	Multiple cellular models	PF 3.28
Acetaminophen toxicity model (GSH contents, cytolysis)	Mouse primary hepatocytes	PF 3.41
Steatosis/Lipid, intracellular accumulation: neutral lipids	Multiple cellular models	PF 3.29
NEW ! NASH model Intracellular lipid accumulation	Primary Human and primary mouse hepatocytes	PF 6.1 ↓ Test Sheet
Lipid, intracellular accumulation: phospholipids	Multiple cellular models	PF 3.30
Mitochondrial Membrane Potential	Multiple cellular models	PF 3.3
MRP2 expression	Primary hepatocytes - sandwich configuration - hepatic tissue	PF 3.5
Cytolysis	Multiple cellular models	PF 3.4
NQO1 expression	Multiple cellular models	PF 3.24
Heme Oxygenase 1 expression	Multiple cellular models	PF 3.25
NAD(P)H / FAD	Multiple cellular models	PF 3.31

ADDITIONAL CAPABILITIES

in vivo studies