Transepithelial resistance and inulin permeability as endpoints in in vitro nephrotoxicity testing.
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.
Duff
Tracey
T
Department of Medicine and Therapeutics, Polwarth and IMS Building, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Carter
Simon
S
Feldman
Gemma
G
McEwan
Gordon
G
Pfaller
Walter
W
Rhodes
Pauline
P
Ryan
Michael
M
Hawksworth
Gabrielle
G
D000826:Animal Testing Alternatives; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005062:European Union; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine; D015262:Xenobiotics / Q000633:toxicity*
D015415:Biomarkers; D015262:Xenobiotics; D007444:Inulin; D016650:Fluorescein-5-isothiocyanate