Indomethacin-induced ileitis is associated with tensiometric, vascular and oxidative changes in the experimental rat model

Eur J Clin Invest. 2005 Apr;35(4):271-8. doi: 10.1111/j.1365-2362.2005.01489.x.

Abstract

Background: Indomethacin-induced enteritis is a model of inflammatory bowel disease.

Materials and methods: To further characterize this model, rats received two injections of indomethacin (7.5 mg kg(-1)) 24 h apart and histological damage of intestinal mucosa, oxidative stress, alterations of intestinal motility and mesenteric vascular bed (MVB) reactivity were investigated after 5 days.

Results: The results show that indomethacin caused several histological and functional changes at the ileal level. In particular, response to carbachol as well as the nonadrenergic-noncholinergic inhibitory response to electrical field stimulation (EFS) was lower in the treated than control rats. Moreover, nitric oxide (NO)-component of the inhibitory response was higher in the treated than control rats. Mesenteric vessels preparations from the treated rats showed increased noradrenaline (NA)-induced perfusion pressure, whereas relaxant responses to acetylcholine, although not significantly reduced in the treated rats, had a higher nitrergic component. This finding suggests that vascular dysfunction may contribute to chronic inflammation. Indomethacin injection also determined acute and severe oxidative stress in ileum mucosa.

Conclusions: In conclusion, our study contributes to further characterize the rat model of indomethacin-induced enteritis and suggests that it is suitable for drug screening in rats, as this model can be obtained in a very short period and is simple and reproducible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology
  • Ileum / drug effects
  • Ileum / pathology
  • Ileum / physiopathology
  • Indomethacin*
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / physiopathology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Mesentery / blood supply
  • Mesentery / drug effects
  • Muscle Contraction / drug effects
  • Muscle, Smooth / physiopathology
  • Norepinephrine / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Adrenergic alpha-Agonists
  • Cholinergic Agonists
  • Carbachol
  • Acetylcholine
  • Norepinephrine
  • Indomethacin