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

Table 1

Test System	HepaRG™
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

References

1. Anthérieu S, Chesné C, Li R, Guguen-Guillouzo C, Guillouzo A. 2012. Optimization of the HepaRG cell model for drug metabolism and toxicity studies. Toxicology in Vitro. 26(8):1278-1285. https://doi.org/10.1016/j.tiv.2012.05.008

2. McGill MR, Yan H, Ramachandran A, Murray GJ, Rollins DE, Jaeschke H. 2011. HepaRG cells: A human model to study mechanisms of acetaminophen hepatotoxicity. Hepatology. 53(3):974-982. https://doi.org/10.1002/hep.24132