Background & Aim: DA-6034 is known to have antiinflammatory activities and exhibits cytoprotective effects in acute gastric injury model. Here we would like to investigate the possible protective role of DA-6034 in indomethacin induced small intes...
Background & Aim: DA-6034 is known to have antiinflammatory activities and exhibits cytoprotective effects in acute gastric injury model. Here we would like to investigate the possible protective role of DA-6034 in indomethacin induced small intestinal damage model and their effect on intestinal permeability.
Methods: Small intestinal damage was induced with indomethacin (15mg/kg). Rats in the treatment group received DA-6034 (30 mg/kg) from day 0 to 2, and indomethacin from day 1 to 2 through intragastric lavage. On the contrary, rats in the control group received only indomethacin from day 1 to 2. On the fourth day, Rats were sacrificed, and small intestine was examined to compare the severity of inflammation in both groups by H&E stain. Intestinal permeability was evaluated by Fluorescein isothiocyanate (FITC)-labeled dextran. Western blot was performed to comfirm the association of DA-6034 with ERK pathway in the prevention of small intestinal injury.
Results: Intestinal permeability was lower in treatment group compared to control group (16204.2±13832.1 vs 30403.7±24012.6, p value <0.05). The inflammation score in the treatment group was lower compared to that in the control group but statistically insignificant (2.6±0.6 vs 2.9±0.3, p=0.11). When the extent of hemorrhage was compared, hemorrhagic lesion in treatment group was broader than that of control group, but was not statistically significant (45±45.5 vs. 43.0±33.8, P=0.88) DA-6034 enhanced the phosphorylation of extracellular signal-regulated kinase (p-ERK) expression in small bowel mucosa (107.4±40.2 vs 64.2±20.4 P value <0.05) and intestinal permeability was negatively correlated with density of ERK expression (r=-0.309, p=0.096).
Conclusion: DA-6034 decrease intestinal permeability in indomethacin induced intestinal injury model via P-ERK pathway.