Indomethacin-induced ileitis is associated with tensiometric, vascular and oxidative changes in the experimental rat model.
BACKGROUND
Indomethacin-induced enteritis is a model of inflammatory bowel disease.


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.
Piepoli
A L
AL
University Medical School, Bari, Italy.
De Salvatore
G
G
De Salvia
M A
MA
Mitolo
C I
CI
Siro-Brigiani
G
G
Marzullo
A
A
Grattagliano
I
I
Mitolo-Chieppa
D
D
Palasciano
G
G
Portincasa
P
P
D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D018679:Cholinergic Agonists; D002217:Carbachol; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin