WP7.2: Improving in vitro/in vivo correlations – Nephrotoxicity

 

WP7.2 Results pdf 61 kB, download the entire summary.

 

The kidney is especially susceptible to toxicity because of its role in excreting compounds, which involves a high blood supply, concentrating, metabolizing and transporting compounds. The focus in WP7.2 was on developing in vitro assays which reflect the role of the kidneys in vivo based on functional parameters including transport and barrier function involving a transepithelial cell layer and transport.

 

In WP7.2 the analysis of 21 ACuteTox reference chemicals (of which five was nephrotoxic) was completed. The functional assay chosen was a transepithelial electrical resistance (TEER) model. In order to assess cytotoxic effects of the test chemicals, the Alamar Blue assay was selected as a viability assay. The renal epithelial (LLC-PK1) cell line was used in both assays under the same conditions. From data obtained the IC20, IC50 and IC80 were calculated for all chemicals tested. The overall results show that the TEER is a more sensitive indicator of toxicity than the Alamar blue assay, with greater sensitivity for nephrotoxic compounds compared to non-nephrotoxic chemicals. However, compounds requiring metabolism, such as diethylene glycol did not show toxicity at the highest concentration tested.