Hepatotoxicity (DILI)

Using pooled primary human hepatocytes and automated high-content imaging tool, the compound is tested whether it induces hepatotoxicity & cell stress, steatosis & phospholipidosis and/or accumulates into lysosomes.
check Protocol

Test concentrations: 2-3

Time points: 1

Replicates: 3

Positive controls

Automated fluorescence microscope analysis

check Deliverables

Viability (cell loss)

Cell membrane permeability (disruption of cell membranes)

Nuclear size and intensity variation, if feasible

Mitochondrial function

Formation of reactive oxygen species (ROS); all as fold compared to vehicle control

Cell count

Decrease in lysosomal staining, compared to vehicle control

Fold of steatotic and phospholipid droplets, compared to vehicle control

check Reporting

Excel report
(full report available per request)

Background

Drug-induced liver injury, DILI, often leading to acute liver failure, can be caused by several mechanisms and poses a challenge in drug discovery. Our approach to assess and mitigate the risk for hepatotoxicity and DILI utilizes automated high-content imaging including evaluation of early signs of hepatotoxicity & cell stress, steatosis & phospholipidosis and lysosomal trapping. The assays employ pooled primary human hepatocytes to achieve complete metabolic function and acknowledge inter-individual variability in humans. With all these parameters evaluated, one can confidently screen for potential DILI risk related to the compounds and identify hazards. Furthermore, to gain further complimentary information, the compounds can be tested for whether they form reactive metabolites or inhibit transporters, which are also mechanisms of liver toxicity.

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