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

Abstract

Introduction: 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. Methods: 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 30 s and then for another 30 s 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-1β (IL-1β) and tumor necrosis factor α (TNF-α). In other groups of animals, jejunal amino acid absorption was determined in vivo at 24 and 48 h post electrocautery. Results: 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-1β 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-α 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 µmol/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). Discussion: This model may be used as an alternative or a complement to chemical models of colitis.