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Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents.
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
Littérature citée [53 références]
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
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
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Licence
Distributed under a Creative Commons Paternité - Pas d'utilisation commerciale - Pas de modification 4.0 International License
