Development of a model for experimental colitis in the rat and cat using acetic acid

MacPherson, Brian Roger (1977) Development of a model for experimental colitis in the rat and cat using acetic acid. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Diffuse, topical application of dilute acetic acid to the serosal surface of the rat colon, or standardized intraluminal (per rectum) instillation of the agent into rat or cat colon, induced a reproducible, diffuse colitis in a dose-response manner. The lesions were reproduced with 100% reliability and were evaluated up to 60 days in the rat, and 21 days in the cat, when healing generally occurred. Histopathological features of this chemically-induced colitis were diffuse ulceration of the distal colon down to the muscularis mucosae or superficial aspect of the submucosa, occurrence of pseudopolyp-like structures, alterations in crypt-depth and mucus secretion, and a transmural, non-specific inflammatory response. Histochemical monitoring revealed an increase in alkaline phosphatase activity as the lesion developed, while mucus staining was markedly decreased. Electron microscopy revealed the mechanism of this agent on the colonic mucosa and indicated initial epithelial sloughing and mucosal edema followed by rapid infiltration of inflammatory cells from submucosal vessels and of erythrocytes from damaged mucosal capillaries. The histopathological pattern observed here was similar to that of an edematous burn response of the colonic mucosa or that induced by other caustic agents, indicating that the colonic mucosa of various species reacts in a similar manner to mechanical or chemical insult. Motility alterations recorded in the colons of cats afflicted with acetic acid-induced lesions, demonstrated a pattern similar to that observed in individuals with inflammatory bowel disease or other diarrheal states. Initial suppression of unstimulated motor activity was followed by a subsequent hyperactive response, while that of urecholine-stimulated activity also demonstrated the initial decrease but returned to near normal values by the end of the experimental period. Suppression of urecholine-stimulated activity during the period of severest diarrhea (greatest ulceration), was not characteristic of that reported in patients with colitis and may indicate some temporary impairment of nervous organization. The opposite was observed during the period of healing and regeneration of the mucosa in animals where the colonic motility was observed to be greatly increased, perhaps reflecting an increased sensitivity. Preliminary trials with corticosteroid and sulfanilamide compounds demonstrated a therapeutic value for the sulfanilamides (Salazopyrin) in significantly reducing the severity of the lesions following pre- and post-induction of colitis treatment in rats.

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