Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents.

Nicolas Esquerre Lilian Basso Caroline Dubuquoy Madjid Djouina 1 Daniel Chappard Catherine Blanpied Pierre Desreumaux 1 Nathalie Vergnolle Cécile Vignal Mathilde Body-Malapel
1 LIRIC - Lille Inflammation Research International Center
Abstract : Irritable bowel syndrome (IBS) is a multifactorial disease arising from a complex interplay between genetic predisposition and environmental influences. To date, environmental triggers are not well known. Aluminum is commonly present in food, notably by its use as food additive. We investigated the effects of aluminum ingestion in rodent models of visceral hypersensitivity, and the mechanisms involved. Visceral hypersensitivity was recorded by colorectal distension in rats administered with oral low doses of aluminum. Inflammation was analyzed in the colon of aluminum-treated rats by quantitative PCR for cytokine expression and by immunohistochemistry for immune cells quantification. Involvement of mast cells in the aluminum-induced hypersensitivity was determined by cromoglycate administration of rats and in mast cell-deficient mice (Kit). Proteinase-activated receptor-2 (PAR2) activation in response to aluminum was evaluated and its implication in aluminum-induced hypersensitivity was assessed in PAR2 knockout mice. Orally administered low-dose aluminum induced visceral hypersensitivity in rats and mice. Visceral pain induced by aluminum persisted over time even after cessation of treatment, reappeared and was amplified when treatment resumed. As observed in humans, female animals were more sensitive than males. Major mediators of nociception were up-regulated in the colon by aluminum. Activation of mast cells and PAR2 were required for aluminum-induced hypersensitivity. These findings indicate that oral exposure to aluminum at human dietary level reproduces clinical and molecular features of IBS, highlighting a new pathway of prevention and treatment of visceral pain in some susceptible patients.
Keywords : proteinase-activated receptor PAR myeloperoxidase MPO immunohistochemistry IHC irritable bowel syndrome IBS colorectal distension CRD aluminum citrate AlCi Visceral Pain Rectum PAR-2 Receptor Sprague-Dawley Rats Nociception Inbred C57BL Mice May-Grünwald Giemsa knockout MGG KO Administration Oral Aluminum Animals Colon Female Hypersensitivity Inflammation Male Mast Cells PAR2 PCR polymerase chain reaction Risk Factors Visceral Hypersensitivity WT wild-type ZnCi zinc citrate mRNA messenger RNA
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [53 références]  Voir  Masquer  Télécharger
https://hal.univ-lille.fr/hal-02148006
Contributeur : Lilloa Université de Lille <>
Soumis le : mercredi 5 juin 2019 - 11:07:56
Dernière modification le : mardi 10 septembre 2019 - 17:20:41

Fichier

MBM33 CGMH2018.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Licence

Distributed under a Creative Commons Paternité - Pas d'utilisation commerciale - Pas de modification 4.0 International License

Identifiants

Collections

UNIV-LILLE | RIIP | RIIP_LILLE

Citation

Nicolas Esquerre, Lilian Basso, Caroline Dubuquoy, Madjid Djouina, Daniel Chappard, et al.. Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents.. Cellular and Molecular Gastroenterology and Hepatology, Philadelphia, PA : American Gastroenterological Association, [2015]-, 2018, Cellular and Molecular Gastroenterology and Hepatology, 7, pp.185-196. ⟨10.1016/j.jcmgh.2018.09.012⟩. ⟨hal-02148006⟩

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

33

Téléchargements de fichiers

50

Contact

Informations

CCSD