CYP- Mediated Toxicity | InSphero

Mechanistic Assays

CYP-mediated Toxicity

Determine involvement of P450 cytochromes in drug-induced hepatotoxicity

The high metabolic competence of 3D InSight™ Human Liver Microtissues make them an ideal tool to study metabolism-mediated toxicity. Because most drugs are metabolized in the liver, the generation of liver damaging metabolites often occurs as the result of phase I metabolism by cytochrome P450 enzymes. Inhibition of these enzymes in 3D InSight™ Human Liver Microtissues can be used as a tool to study CYP-driven mechanisms of hepatotoxicity.

  • Ensure metabolite profile better reflects that of native liver with robust, long-lived CYP expression and activity
  • Discriminate between parent compound toxicity and metabolite-mediated toxicity by inhibition of cytochrome P450 enzymes
  • Ensure reproducibility at higher throughput with standardized, pre-qualified models in 96-well format

Example Data

Aflatoxin B1 toxicity is mediated through cytochrome P450 activity. The effect of aflatoxin B1 with or without CYP-inhibition on the cell viability of 3D InSight™ Human Liver Microtissues was evaluated. Following the compound exposure in presence or absence of the pan-CYP-inhibitor, cell viability was assessed by measuring the intracellular ATP content using the CellTiter-Glo® Assay (Promega, USA). Aflatoxin B1 exposure resulted in an IC50 value of 0.22 µM. The presence of pan-CYP-inhibitor inhibited Aflatoxin B1 metabolism and thus prevented Aflatoxin B1 toxicity.

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