Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents.
Administration, Oral
Aluminum
/ administration & dosage
Animals
Colon
/ drug effects
Female
Hypersensitivity
/ pathology
Inflammation
/ pathology
Male
Mast Cells
/ drug effects
Mice, Inbred C57BL
Mice, Knockout
Nociception
/ drug effects
Rats, Sprague-Dawley
Receptor, PAR-2
/ metabolism
Rectum
/ drug effects
Visceral Pain
/ metabolism
AlCi, aluminum citrate
CRD, colorectal distension
IBS, irritable bowel syndrome
IHC, immunohistochemistry
KO, knockout
MGG, May-Grünwald Giemsa
MPO, myeloperoxidase
Mast Cells
PAR, proteinase-activated receptor
PAR2
PCR, polymerase chain reaction
Risk Factors
Visceral Hypersensitivity
WT, wild-type
ZnCi, zinc citrate
mRNA, messenger RNA
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2019
2019
Historique:
received:
27
02
2018
accepted:
12
09
2018
entrez:
12
12
2018
pubmed:
12
12
2018
medline:
30
4
2019
Statut:
epublish
Résumé
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 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.
Sections du résumé
Background & Aims
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.
Methods
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
Results
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.
Conclusions
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.
Identifiants
pubmed: 30534582
doi: 10.1016/j.jcmgh.2018.09.012
pii: S2352-345X(18)30134-6
pmc: PMC6280602
pii:
doi:
Substances chimiques
Receptor, PAR-2
0
Aluminum
CPD4NFA903
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
185-196Commentaires et corrections
Type : CommentIn
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