Here, we demonstrate how the PhysioMimix DILI assay kit: Human 24 and PhysioMimix OOC Single-organ System captures more complex mechanisms of human DILI than traditional preclinical approaches to reduce the risk of unforeseen event detection in the clinic.

The evaluation was performed using the tool compounds troglitazone and amiodarone. Troglitazone is a well-known example of a drug withdrawn post-marketing due to fatal DILI events. A range of mechanisms have since been associated with its hepatotoxicity, including oxidative stress, reactive metabolite generation, mitochondrial dysfunction, cholestasis and steatosis. Amiodarone is still in clinical use for advanced heart disease, although liver toxicity has been identified in 1% of treated patients. Damage to lysosomal and mitochondrial function, followed by micro-vesicular steatosis are considered the key mechanisms of hepatotoxicity.

Using the PhysioMimix DILI assay kit: Human 24, clinically relevant signatures of hepatotoxicity were captured using multiple soluble and tissue markers, demonstrating the assay’s value when integrated into preclinical toxicology workflows to ease reliance on animals and decrease hepatotoxicity risks in the clinic.

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