Hepatotoxicity

 

XenoTech hepatotoxicity studies assess the risk that a test article may cause toxicity in human, non-human or immortalized human hepatocytes. Critical factors that we consider when performing such studies include:

  • Confluent, morphologically normal cells that have been allowed to establish cell-to-cell contact
  • Examining potential toxicity by parent compound(s)
  • Experimental conditions that allow for metabolism-dependent toxicity to be observed
  • Analyzing preparations from multiple humans due to high inter-individual variability (when using human hepatocytes).

It is important to measure endpoints that are well-characterized and understood, carefully choose concentrations of test articles, and treat cells with different concentrations in order to generate concentration-response profiles for early-stage compounds.  XenoTech performs the LDH (lactate dehydrogenase)-release assay, Alamar Blue assay and qRT-PCR analysis of mRNA to assess toxicity in vitro.  This information is then used to generate concentration-response profiles with pharmacologically-relevant concentrations of test articles.  In addition, any morphological changes of the cultures are documented with photomicrographs for reference.