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

AbstractBACKGROUND: 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.
AuthorsA L Piepoli, G De Salvatore, M A De Salvia, C I Mitolo, G Siro-Brigiani, A Marzullo, I Grattagliano, D Mitolo-Chieppa, G Palasciano, P Portincasa
JournalEuropean journal of clinical investigation (Eur J Clin Invest) Vol. 35 Issue 4 Pg. 271-8 (Apr 2005) ISSN: 0014-2972 [Print] England
PMID15816997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-Agonists
  • Cholinergic Agonists
  • Carbachol
  • Acetylcholine
  • Norepinephrine
  • Indomethacin
Topics
  • Acetylcholine (metabolism)
  • Adrenergic alpha-Agonists (pharmacology)
  • Animals
  • Carbachol (pharmacology)
  • Cholinergic Agonists (pharmacology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gastrointestinal Motility (drug effects, physiology)
  • Ileum (drug effects, pathology, physiopathology)
  • Indomethacin
  • Inflammatory Bowel Diseases (pathology, physiopathology)
  • Intestinal Mucosa (drug effects, pathology)
  • Mesentery (blood supply, drug effects)
  • Muscle Contraction (drug effects)
  • Muscle, Smooth (physiopathology)
  • Norepinephrine (pharmacology)
  • Oxidative Stress (drug effects, physiology)
  • Rats
  • Rats, Wistar
  • Synaptic Transmission (drug effects, physiology)

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