Vulnerable Sites and Changes in Mucin in the Rat Small Intestine After Non-steroidal Anti-inflammatory Drugs Administration

Abstract

The location of mucosal damage and changes in mucin content in the rat small intestine following administration of non-steroidal anti-inflammatory drugs (NSAIDs) have not been well elucidated. After subcutaneous administration of loxoprofen sodium (10-40 mg/kg), the small intestinal mucosa of male Wistar rats was evaluated macroscopically, histologically, and immunohistochemically by measuring the total mucin content and immunoreactivity for anti-mucin monoclonal antibody, HCM31, 1, 3, 7, and 14 days later. Changes in the number of enterobacteria invading the mucosa around the lesions were also determined. Loxoprofen sodium induced erosions and ulcers along the mesenteric margin of the distal jejunum. Early (≤6 h) mucosal lesions were small and round, located between the branches of the mesenteric arteries. In the jejunum, there was a transient increase in the total mucin content, and HCM31-positive mucin in the mucosa around the ulcers increased significantly on days 3 and 7, but in the ileum there were no marked changes and few ulcers. Bacterial translocation following loxoprofen sodium administration significantly increased, according to the site of the intestinal lesions. Vascularly compromised sites along the jejunal mesenteric margin are vulnerable to NSAIDs-induced damage and show increased numbers of enterobacteria in the NSAIDs-treated mucosa. Increased sialomucin content in the mucus around the lesions may play an important role in the healing of NSAIDs-induced intestinal lesions.