Effects of the pesticide clorpyrifos on an in vitro model of intestinal barrier

Toxicol In Vitro. 2007 Mar;21(2):308-13. doi: 10.1016/j.tiv.2006.08.015. Epub 2006 Sep 16.

Abstract

Clorpyrifos (CPF), one of the most widely used organophosphorothionate pesticide can be detected as residues in food and drinking water; therefore the oral route is the major route of exposure for the general population, including children, following household use of this insecticide. Aim of this work was to investigate the possible acute cytotoxic effects of CPF on intestine and the integrity of the epithelial barrier, using Caco-2/TC7 cells as intestinal in vitro model. High level of CPF found inside the cells, corresponding to about 80% of the nominal concentration tested (30, 50 and 250microM), chosen as representative of the concentrations attainable in the intestinal lumen after actual levels of human oral exposure. In these conditions, no cytotoxicity in terms of cellular viability was observed. However, at the highest CPF nominal concentration (250microM) the impairment of barrier integrity was evidenced, due only to the parent compound, since no CPF metabolites could be detected in our experimental conditions. CPF itself was demonstrated to interfere with the tight junction on this in vitro model of epithelial intestinal cells, altering the barrier integrity and very likely the absorption of other co-administered chemicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Survival / drug effects
  • Chlorpyrifos / pharmacokinetics
  • Chlorpyrifos / toxicity*
  • Cytochrome P-450 CYP3A / physiology
  • Electric Impedance
  • Humans
  • Insecticides / toxicity*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Tight Junctions / drug effects

Substances

  • Insecticides
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Chlorpyrifos