New Ulcerative Colitis Model Induced by Sulfhydryl Blockers in Rats and the Effects of Antiinflammatory Drugs on the Colitis.

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  • Satoh Hiroshi
    Pharmaceutical Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
  • Sato Fumihiko
    Pharmaceutical Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
  • Takami Kenji
    Drug Safety Research Laboratories, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
  • Szabo Sandor
    Department of Pathology, Harvard Medical School

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  • New Ulcerative Colitis Model Induced by

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We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 μl of 3% N-ethylmaleimide (NEM)or iodoacetamide (IA)was introduced into the colon via a Nelaton''s catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1 3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 73 (4), 299-309, 1997

    公益社団法人 日本薬理学会

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