Liver Toxicity Imaging Analysis

Liver Toxicity Imaging Analysis

The liver is a central metabolic organ and is easily damaged by chemicals and/or their metabolites entering the body. Drugs have a special risk of causing drug-induced liver injury (DILI). Liver toxicity is an important reason for withdrawal of drugs from the market, which brings huge economic losses to pharmaceutical companies. Therefore, it is important to create an in vitro model that can effectively evaluate liver toxicity, and to identify and eliminate potentially problematic compounds in the early stages of drug discovery.

 Stages of liver damage.Figure 1. Stages of liver damage.

Liver Toxicity Imaging Analysis

The monolayer culture of primary hepatocytes to determine the effect of drugs on cell viability provides an overall measure of liver toxicity, but this method cannot reveal the specific mechanism of drug toxicity due to the lack of 3D tissue and non-parenchymal cells. CD BioSciences can not only use traditional monolayer cell models to evaluate the liver toxicity effects of test compounds, but also use 3D liver tissue models to evaluate the liver toxicity effects of test compounds. The 3D liver tissue model is formed by culturing hepatocytes and non-parenchymal cells at a nearly physiological ratio using the transwell method.  

Analysis method High content imaging
Analysis instrument High content imaging system
Cell models Monolayer format:
HepG2, HepaRG, primary human hepatocytes
3D cell culture model format:
HepG2, primary human hepatocyte 3D cell models, primary rodent hepatocyte 3D cell models, custom models available on request
Toxicity markers Cell viability, apoptosis, reactive oxygen species generation, steatosis and phospholipidosis, cholestasis, fibrosis, mitochondrial function, glutathione depletion
Time points Monolayer models: 24 h, 48 h
3D cell models: 24 h, 48 h, 7 days, 14 days
Other time points available on request
Sample requirements 150 µL of a DMSO solution to achieve 100x Cmax or equivalent amount in solid compound

Liver Toxicity Imaging Analysis Workflow

CD BioSciences uses high-content screening to perform imaging analysis of liver toxicity. The detailed steps are as follows:

Step 1

For 3D cell models, grown to approximately 200 μm in diameter. Adherent monolayers cultured to confluence.

Step 2

Treatment with test compounds.

Step 3

Labeling with fluorescent probes.

Step 4

For 3D cell models, tissue clearing is applied to render 3D cell models transparent.

Step 5

High content imaging is conducted on well plates.

Step 6

Images are analyzed to quantify assay endpoints.

Delivery

Minimum effective concentration (MEC)
Dose response curves
Evaluation of statistical significance of results with respect to vehicle and positive control
AC50 value for each measured parameter
heatmaps normalized to Cmax

Our Advantages

  • Multiple liver toxicity markers
  • Provide three-dimensional information about liver toxicity
  • Experienced scientists provide experimental consultation
  • Reduced workload and cost

CD BioSciences has a professional team and advanced imaging equipment. We provide you with liver toxicity imaging analysis services by 2D monolayer liver cell models and 3D liver tissue models. We can adjust the liver toxicity endpoint according to your needs and design a personalized analysis plan for you. If you have any needs  for liver toxicity imaging analysis, please feel free to contact us.

References
  1. Asilar E, Hemmerich J, Ecker G F. Image based liver toxicity prediction[J]. Journal of chemical information and modeling, 2020, 60(3): 1111-1121.
  2. Bale S S, Vernetti L, Senutovitch N, et al. In vitro platforms for evaluating liver toxicity[J]. Experimental biology and medicine, 2014, 239(9): 1180-1191.

*If your organization requires the signing of a confidentiality agreement, please contact us by email.

Please note: Our services can only be used for research purposes. Do not use in diagnostic or therapeutic procedures!

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