title: Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats.
abstract: The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs), multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier) during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC)-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR) and localization (using immunofluorescence) of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs). In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning) but not at day 60 (adulthood). At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal epithelium may be a risk factor for digestive inflammatory diseases.
authors.affiliation: Peritox Laboratory, EA4285 UMI01 Ineris, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Joly Condette
authors.affiliation: Peritox Laboratory, EA4285 UMI01 Ineris, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France.
authors.forename: Hafida
authors.initials: H
authors.lastname: Khorsi-Cauet
authors.affiliation: INSERMU1088, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France; Biochemistry Laboratory, Human Biology Centre, Amiens University Hospital, Amiens, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Morlière
authors.affiliation: EA4666, Jules Verne University of Picardy, Amiens, France.
authors.forename: Luciane
authors.initials: L
authors.lastname: Zabijak
authors.affiliation: Peritox Laboratory, EA4285 UMI01 Ineris, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Reygner
authors.affiliation: Peritox Laboratory, EA4285 UMI01 Ineris, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Bach
authors.affiliation: Peritox Laboratory, EA4285 UMI01 Ineris, Faculty of Medicine, Jules Verne University of Picardy, Amiens, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gay-Quéheillard
mesh_terms: D000367:Age Factors; D000818:Animals; D004390:Chlorpyrifos / Q000633:toxicity*; D057167:Claudins / Q000378:metabolism; D003911:Dextrans; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005455:Fluorescent Antibody Technique; D007306:Insecticides / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D018811:Maternal Exposure; D062793:Occludin / Q000378:metabolism; D010539:Permeability / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013050:Spectrometry, Fluorescence; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D057167:Claudins; D003911:Dextrans; D007306:Insecticides; D062793:Occludin; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D004390:Chlorpyrifos