Translational Toxicity | InSphero

DILI Prediction

Translational Toxicity

Compare pre-clinical susceptibility to drug-induced hepatotoxicity in different species

Drug-Induced Liver Injury (DILI) due to species-specific susceptibilities mediated by xenobiotic metabolism and/or the occurrence of idiosyncratic drug hepatotoxicity are among the most frequent type of adverse drug effects. Early identification of species-specific, adverse drug effects on the liver are important for increasing drug development efficiency. InSphero 3D InSight™ Liver Microtissues, developed using primary hepatocytes from human (multi- or single-donor) as well as animal species commonly used in toxicity testing (monkey, dog, and rat) are available as monoculture hepatocyte models or co-culture models with Kupffer cells or NPCs . We provide a specially formulated culture media that allows the direct comparison of obtained IC50 values among species, making this system an invaluable tool for DILI detection and the evaluation of pre-clinical species-specific drug effects in 3D liver microtissues.

  • Compare DILI in human, rat, dog, and monkey 3D primary liver microtissue models
  • Perform translational toxicity studies in advanced 3D liver models using a standardized 3-7 day, repeat-dosing protocol
  • Normalize differential drug/media-component binding effects with a newly developed universal testing medium used for all species

Example Data

Viability dose-response curve of Human and Dog Liver Microtissues upon treatment with Aflatoxin B1. Liver microtissues were exposed to increasing concentration of Aflatoxin B1 for 7 days with one re-dosing. 3D InSight™ Dog Liver Microtissues showed an IC50 value of 0.02 µM, which was 5.5-fold lower than for Human Liver Microtissues (IC50: 0.11 µM). This is in line with the reported high sensitivity of dogs to Aflatoxin B1 in vivo (1-3). Viability was accessed with the ATP assay (Promega CellTiter-Glo®).

References

  1. Newberne et al, Veterinary Pathology (1966)
  2. Ambrecht et al, Toxicology and Applied Pharmacology (1971)
  3. O’Brien et al, Chemico-Biological Interactions (2004)

Request Additional Resources

Brochure: Solutions for Toxicology

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Poster: Cross-species Toxicity Testing – SOT2017

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