Characteristics of ulcers of the small bowel induced by non-steroidal anti-inflammatory drugs in the rat: implications for clinical practice.

Small bowel ulcers were created in the rat after the oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). Of the six NSAIDs tested, indomethacin and diclofenac alone were associated with such damage which did not occur in a simple dose-related fashion. Bacteria were observed by electron microscopy in an active state of division in the base of the ulcers. When grown aerobically these were shown to be strains of Escherichia coli and Proteus mirabilis. Anatomically, NSAID-induced ulcers were found throughout the length of the bowel although more abundant in the proximal half. In vivo and in vitro sensitivity to antibiotics suggested that in addition to the bacteria identified, anaerobic beta-lactamase-producing organisms also have an important role in ulcer production in this model. This rat model of NSAID-induced gut toxicity is discussed in relation to the human situation, particularly for patients who take NSAIDs and who have an iron-deficiency anaemia and blood in their faeces, but no lesions in either the upper or lower bowel.