Dextran sulfate sodium induces pan-gastroenteritis in rodents: implications for studies of colitis

Dextran sulfate sodium is widely used to induce colitis in rodents. Though given orally in drinking water, this agent is widely believed to produce injury through direct toxic effects on the epithelium, and it has been assumed to produce damage and inflammation only in the colon. Given the apparent toxic effects of dextran sodium sulfate on epithelial cells, its administration orally, and the anticoagulant properties of this agent, we hypothesized that significant damage and inflammation would be produced in regions of the digestive tract proximal to the colon. Groups of rats or mice received DSS (5%) in the drinking water for up to 7 days. Tissues were harvested at various time-points for blind evaluation of damage, and measurement of several markers of inflammation. In both rats and mice given DSS, significant damage and inflammation was produced in the stomach, small intestine and colon. Significant granulocyte infiltration was apparent in all tissues by day 3 of DSS ingestion. Bleeding was evident throughout the small intestine and colon. These studies clearly demonstrate that DSS, when administered orally in drinking water, produces a pan-gastroenteritis, rather than the damage and inflammation being limited to the colon. The damage and inflammation in the stomach and small intestine could contribute to changes in body weight, stool consistency and bleeding, all of which are commonly used as indices of severity of colitis. Beneficial or detrimental effects of therapeutic interventions could be attributable, at least in part, to modulation of injury and inflammation proximal to the colon.