A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction

Tatsuhiro Masaoka, Tim Vanuytsel, Christophe Vanormelingen, Sebastien Kindt, Shadea Salim Rasoel, Werend Boesmans, Gert De Hertogh, Ricard Farré, Pieter Vanden Berghe, Jan Tack

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and Aims: Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called "post-inflammatory" FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60% of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals. Methods: Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine. Results: Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats. Conclusions: Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of "low-grade inflammatory" FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.

Original languageEnglish
Article numbere95879
JournalPLoS One
Volume9
Issue number5
DOIs
Publication statusPublished - 2014 May 12
Externally publishedYes

Fingerprint

Medical problems
diabetes
Animals
Animal Models
animal models
Nitric Oxide Synthase Type II
Rats
rats
Inflammation
inflammation
Messenger RNA
Infiltration
Myenteric Plexus
Gastrointestinal Diseases
Hematoxylin
Eosine Yellowish-(YS)
Hyperglycemia
Dilatation
plexus
Immunohistochemistry

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Masaoka, T., Vanuytsel, T., Vanormelingen, C., Kindt, S., Salim Rasoel, S., Boesmans, W., ... Tack, J. (2014). A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction. PLoS One, 9(5), [e95879]. https://doi.org/10.1371/journal.pone.0095879

A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction. / Masaoka, Tatsuhiro; Vanuytsel, Tim; Vanormelingen, Christophe; Kindt, Sebastien; Salim Rasoel, Shadea; Boesmans, Werend; De Hertogh, Gert; Farré, Ricard; Vanden Berghe, Pieter; Tack, Jan.

In: PLoS One, Vol. 9, No. 5, e95879, 12.05.2014.

Research output: Contribution to journalArticle

Masaoka, T, Vanuytsel, T, Vanormelingen, C, Kindt, S, Salim Rasoel, S, Boesmans, W, De Hertogh, G, Farré, R, Vanden Berghe, P & Tack, J 2014, 'A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction', PLoS One, vol. 9, no. 5, e95879. https://doi.org/10.1371/journal.pone.0095879
Masaoka, Tatsuhiro ; Vanuytsel, Tim ; Vanormelingen, Christophe ; Kindt, Sebastien ; Salim Rasoel, Shadea ; Boesmans, Werend ; De Hertogh, Gert ; Farré, Ricard ; Vanden Berghe, Pieter ; Tack, Jan. / A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction. In: PLoS One. 2014 ; Vol. 9, No. 5.
@article{06258ca53d074ed79f610517ebd33309,
title = "A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction",
abstract = "Background and Aims: Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called {"}post-inflammatory{"} FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60{\%} of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals. Methods: Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine. Results: Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats. Conclusions: Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of {"}low-grade inflammatory{"} FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.",
author = "Tatsuhiro Masaoka and Tim Vanuytsel and Christophe Vanormelingen and Sebastien Kindt and {Salim Rasoel}, Shadea and Werend Boesmans and {De Hertogh}, Gert and Ricard Farr{\'e} and {Vanden Berghe}, Pieter and Jan Tack",
year = "2014",
month = "5",
day = "12",
doi = "10.1371/journal.pone.0095879",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction

AU - Masaoka, Tatsuhiro

AU - Vanuytsel, Tim

AU - Vanormelingen, Christophe

AU - Kindt, Sebastien

AU - Salim Rasoel, Shadea

AU - Boesmans, Werend

AU - De Hertogh, Gert

AU - Farré, Ricard

AU - Vanden Berghe, Pieter

AU - Tack, Jan

PY - 2014/5/12

Y1 - 2014/5/12

N2 - Background and Aims: Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called "post-inflammatory" FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60% of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals. Methods: Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine. Results: Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats. Conclusions: Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of "low-grade inflammatory" FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.

AB - Background and Aims: Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called "post-inflammatory" FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60% of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals. Methods: Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine. Results: Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats. Conclusions: Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of "low-grade inflammatory" FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.

UR - http://www.scopus.com/inward/record.url?scp=84901283561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901283561&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0095879

DO - 10.1371/journal.pone.0095879

M3 - Article

C2 - 24819503

AN - SCOPUS:84901283561

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e95879

ER -