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Rapid decrease in transepithelial electrical resistance of human intestinal Caco-2 cell monolayers by cytotoxic

A Narai1, S Arai, M Shimizu

  • 1Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113, Japan.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|July 27, 2010
PubMed
Summary

Transepithelial electrical resistance (TEER) offers a sensitive method for detecting membrane-damaging toxicants. This assay detects cellular damage earlier than traditional lactate dehydrogenase release assays.

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Area of Science:

  • Cell Biology
  • Toxicology
  • Biophysics

Background:

  • Assessing cytotoxic effects on cell monolayers is crucial for drug development and safety testing.
  • Current methods like lactate dehydrogenase release assay detect cell damage at later stages.
  • There is a need for sensitive and rapid methods to evaluate membrane-perturbing toxicants.

Purpose of the Study:

  • To investigate the utility of transepithelial electrical resistance (TEER) as an early indicator of membrane damage caused by cytotoxic agents.
  • To compare the sensitivity and timing of TEER measurements with lactate dehydrogenase release for assessing cell membrane integrity.

Main Methods:

  • Human intestinal Caco-2 cell monolayers were cultured on permeable filters.
  • Monolayers were exposed apically to cytotoxic membrane perturbents (benzalkonium chloride, saponin).
  • Transepithelial electrical resistance (TEER) and lactate dehydrogenase (LDH) release were measured over time.

Main Results:

  • Apical exposure to toxicants caused a rapid decrease in TEER.
  • TEER decrease occurred at lower toxicant concentrations and earlier time points compared to LDH release.
  • TEER reduction correlated with increased transepithelial permeability and cytoskeletal alterations.

Conclusions:

  • TEER measurement is a sensitive and rapid method for evaluating membrane-perturbing toxicants.
  • TEER changes reflect early-stage membrane damage and disruption of tight junctions.
  • This technique offers advantages over traditional assays for early toxicity screening.