Hepatotoxicity/Cytotoxicity Assays

The hepatotoxicity/cytotoxicity assays provide a means to measure cell death due to the cytotoxic effect of a test compound. We provide hepatotoxicity/cytotoxicity assays for all small molecule formulations such as pharmaceuticals, industrial chemicals and consumer products.

Our hepatotoxicity/cytotoxicity assays use a genetically modified version of the metabolically active immortalized human liver cell line HepaRG™, created with our proprietary CompoZr® zinc finger (ZFN) nuclease technology.

Hepatotoxicity is the leading cause of late-stage drug attrition and there is great interest in understanding the potential for a drug to cause liver damage. Primary human hepatocytes are the gold standard for these types of studies, but limited availability, high cost, donor-to-donor variability and other concerns limit their application on a broader scale. Apart from human hepatocytes, HepaRG cells are the most metabolically active liver cell line described to date and have the potential for use as a viable surrogate in many functional liver assays, including hepatotoxicity testing.

We offer hepatotoxicity screening with a variety of individual or multiple endpoints. Cytotoxicity is typically assessed using MTT, but other endpoints may be substituted, including neutral red, LDH or ATP depletion. Follow-up assays can be added to determine whether cell death occurs via necrosis or apoptosis. 
 

 Hepatotoxicity Assay Protocol

 
Test System HepaRG, liver cell, clone 5F (human)
Test Compound Concentration 1 -300 µM in half log increments, or custom
Replicates 3
Assay Length 48 hours
Controls Vehicle (0.1% DMSO) Chlorpromazine
Analysis Method MTT, absorbance
Data Delivery IC50

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References

  • Anthérieu S et al. (2012) Optimization of the HepaRG cell model for drug metabolism and toxicity studies, Toxicol In Vitro 26, 1278-1285
  • McGill et al. (2011) HepaRG™ cells: a human model to study mechanisms of acetaminophen hepatotoxicity, Hepatology 53, 974-982