Transepithelial resistance and inulin permeability as endpoints in in vitro nephrotoxicity testing

Altern Lab Anim. 2002 Dec:30 Suppl 2:53-9. doi: 10.1177/026119290203002S08.

Abstract

Transepithelial electrical resistance (RT) and the flux of fluorescein isothiocyanate (FITC) across Madin Darby canine kidney (MDCK) strain 1 cells and porcine epithelial kidney (LLC-PK1) monolayers were compared between three laboratories for a range of nephrotoxins. The precision of the REMS AutoSampler was similar to that of the Ussing chamber and the ENDOHM technique, but superior to using chopstick electrodes, for measurements of resistance. The nephrotoxins used were selective for the proximal tubule, and in all cases, LLC-PK1 cells were more sensitive than MDCK cells. In most cases, change in RT was a more sensitive indicator of damage than alterations in FITC flux. The REMS system provides high intra-plate precision for RT measurements and is a higher throughput system, which is applicable to screening for nephrotoxicity in vitro.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Testing Alternatives*
  • Animals
  • Biomarkers
  • Cell Line
  • Dogs
  • Electric Impedance
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology
  • European Union
  • Fluorescein-5-isothiocyanate / metabolism
  • In Vitro Techniques
  • Inulin / metabolism*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / pathology
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Swine
  • Xenobiotics / toxicity*

Substances

  • Biomarkers
  • Xenobiotics
  • Inulin
  • Fluorescein-5-isothiocyanate