The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model

BACKGROUND/AIMS: DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. METHODS: Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. RESULTS: The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. CONCLUSIONS: DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Complement and Integrative Approach in Gut Health and Immunologic Disease / 한양의대학술지

The intestine is an organ involved with absorbing, processing, and transporting food into the body. However, if one were to assess the immunological portion of the intestine and compare it with better-known immunologically functioning organs such as the spleen, the intestine would be found to be the largest such organ and the extent of its immunologic function would be found to be equally proportionate. The mucosal surface of the intestine has the ability to respond to effector cells capable of protecting the host from potentially harmful organisms or local antigens. When there is increased intestinal permeability (Leaky gut syndrome), pathogenic bacteria and its products, toxins, antigens, chemicals and incompletely digested food penetrate the intestinal epithelium and are transported throughout the body. They activate the immune system and effect the pathophysiology of acute and chronic inflammatory disease and autoimmune disease. Therefore, by a better understanding of the importance of gut barrier function and the pathophysiology of gut related immunologic disease, we can make helpful suggestions for achieving optimal intestinal health.