The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.
OBJECTIVE
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.
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Dong Shin
DS
Kwak
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Oh Young
OY
Lee
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Kang Nyeong
KN
Lee
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Dae Won
DW
Jun
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Hang Lak
HL
Lee
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Byung Chul
BC
Yoon
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea.
Ho Soon
HS
Choi
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004751:Enteritis / Q000139:chemically induced / Q000503:physiopathology; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000633:toxicity; D007421:Intestine, Small / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; C121889:recoflavone; D007213:Indomethacin
DA-6034; Intestinal permeability; Leaky gut syndrome; Small intestinal injury model