The Pathophysiology of Nonsteroidal Anti-inflammatory Drug Induced Enteropathy in Rat

Kim, You Sun; Lee, Na Rae; Kim, Joo Sung; Jung, Hyun Chae; Song, In Sung; Kim, Chung Yong

Abstract

BACKGROUND/AIMS
The pathophysiology of nonsteroidal anti-inflammatory drug (NSAID) induced enteropathy is still uncertain. It is proposed that an increase in intestinal permeability due to NSAID plays an important role in it. We have investigated the change of gastrointestinal permeability after administration of NSAID to rats. Prostagrandin E2 (PGE2) level and gene expression of COX enzyme were also investigated.
METHODS
After administration of indomethacin 15 mg/kg, gastrointestinal permeability was measured at the 1st day, 3rd day, 7th day, and 14th day using mixture of sucrose, lactulose and mannitol. We evaluated PEG2 level by RIA method and gene expression of COX enzyme by reverse transcription-polymerase chain reaction. RESULTS: The gastric permeability was increased as 7 times as baseline (p<0.01) at 1st day and then normalized at 7th day. On the other hand, the small intestinal permeability was peaked at 3rd day and normalized at 14th day. PGE2 level was increased at 1st day in both gastropathy and enteropathy lesions and the new gene expression of COX-2 enzyme was confirmed. CONCLUSIONS: The increased small intestinal permeability by NSAID and aggravation through consequent enterohepatic recirculation of NSAID may act as an important mechanism in NSAID-induced enteropathy. The PGE2 produced by COX-2 may play an important role in the healing process of NSAID-induced gastroenteropathy.