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

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Abstract

Background and Aims

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

We would like to express our sincere thanks to S. Sugawara, M. Hashimura, and Y. Numata for their technical assistance. This work was supported in part by grants from the Shin-Caterpillar Mitsubishi Co., and the Integrative Research Project of the Graduate School of Medical Sciences, Kitasato University. The authors report no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan

    Tomohisa Iwai, Mitsuhiro Kida, Yoichi Saegusa & Katsunori Saigenji

  2. Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, 1-15-1, Kitasato, Sagamihara, Kanagawa, 228-8555, Japan

    Takafumi Ichikawa, Yukinobu Goso & Kazuhiko Ishihara

  3. Department of Pathology, Kitasato University School of Medicine, Kitasato, Sagamihara, Japan

    Isao Okayasu

Authors
  1. Tomohisa Iwai
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  2. Takafumi Ichikawa
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  8. Kazuhiko Ishihara
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Correspondence to Kazuhiko Ishihara.

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Iwai, T., Ichikawa, T., Kida, M. et al. Vulnerable Sites and Changes in Mucin in the Rat Small Intestine After Non-steroidal Anti-inflammatory Drugs Administration. Dig Dis Sci 55, 3369–3376 (2010). https://doi.org/10.1007/s10620-010-1185-6

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  • DOI: https://doi.org/10.1007/s10620-010-1185-6

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