Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acid-perfusion model in rats.
One of the important problems in experimentally induced small intestinal lesions is that there is no reproducible model of diffuse and stable mucosal lesion. In this paper, we studied in detail the effects of continuous perfusion of various concentrations of acetic acid on the rat small intestinal mucosa. In order to evaluate its applicability for screening of the preventive effect of drugs on gut damage, we also evaluated the efficacy of corticosteroid pretreatment in preventing acetic acid-induced mucosal lesion. Male Sprague-Dawley rats were fasted for 12 hr, and the small intestinal lumen was perfused with 1%, 1.5%, 2.5%, 3%, 3.75% (pH 2.4-2.6) acetic acid or saline (control) at 1 ml/min for 15 min. In separate experiments, the effect of preadministration of budesonide (0.5 or 0.75 mg/kg/day) and prednisone (0.75 mg/kg/day) on 1.5% acetic acid-induced mucosal damage was investigated. Macroscopic and microscopic lesions occurred diffusely in a concentration-dependent fashion. Histological findings revealed signs of transmural inflammation characterized by mucosal-submucosal edema, ulceration, and neutrophil infiltration. Mucosal-submucosal height had an inverse relation with the acetic acid concentrations perfused. Myeloperoxidase activity levels increased several-fold in the acetic acid-perfused groups. Corticosteroid pretreatment prevented microscopic damage and was associated with reduction of MPO activity levels in 1.5% acetic acid-perfused rats. We conclude that this simple and reproducible model could be applied for the screening of new drugs in the gastrointestinal tract in which large numbers of animals are taken into account.
Pacheco
I
I
First Department of Internal Medicine, Akita University School of Medicine, Akita City, Japan.
Otaka
M
M
Jin
M
M
Sasahara
H
H
Iwabuchi
A
A
Odashima
M
M
Konishi
N
N
Wada
I
I
Masamune
O
O
Watanabe
S
S
D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D019819:Budesonide; D009195:Peroxidase; D019342:Acetic Acid; D011241:Prednisone