Troubleshooting in animal models of colitis: The use of a novel electrocautery model

Experimental colitis induced by chemical agents leads to upregulation of inflammatory cytokines in distant unaffected small intestine and to a decrease in nutrient absorption. To preclude any possible proximal diffusion of these chemicals, we designed a novel method for ulcer induction in the colon by electrocautery.

Under light anesthesia, a colonic ulcer was induced in rats by a special electrocautery probe introduced in the descending colon through the rectum allowing the injection of a controlled electrolytic current. A direct current (3-7 mA) was delivered through the electrodes for 30s and then for another 30s after reversing the polarity of the electrodes. Then, the probe was moved for a distance of +/-0.5 cm and the current injection was repeated. Rats were sacrificed at various time intervals after ulcer induction (3-96 h). Samples from colon and jejunum were taken for histological assessment and determination, by ELISA, of the levels of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). In other groups of animals, jejunal amino acid absorption was determined in vivo at 24 and 48 h post electrocautery.

A colonic ulcer persisted for 72 h after cauterization. A significant upregulation of the levels of different cytokines was observed in the colon and jejunum post cauterization and persisted for at least 48 h. In the jejunum, IL-1beta increased from 81+/-9 to 652+/-110 (p<0.01) and 243+/-47 (p<0.05) pg/mg protein at 24 and 48 h, respectively. Similarly, jejunal TNF-alpha levels increased by approximately 2 folds at 24 and 48 h post ulcer induction (p<0.05). A similar but higher increase in cytokines was observed in the colon. Jejunal alanine absorption (0.2+/-0.02 micromol/20 min/cm) decreased significantly at 24 and 48 h after colitis induction (0.12+/-0.01 and 0.14+/-0.02, respectively; p<0.01).

This model may be used as an alternative or a complement to chemical models of colitis.