Effects of indomethacin on the rat small intestinal mucosa: immunohistochemical and biochemical studies using anti-mucin monoclonal antibodies.
BACKGROUND
The luminal surface of the gastrointestinal tract is covered by a viscoelastic gel layer that acts as a protective barrier against the intraluminal environment. Because the situation of the small intestine has not been elucidated to the same degree as other sections, in this study, we investigated the effects of indomethacin on the rat small intestinal mucosa.


METHODS
Male Wistar rats were given indomethacin 10 mg/kg s-c and sacrificed 1, 3, 7, or 14 days later. The small intestine was opened along the anti-mesenteric side, and examined macroscopically. Total mucin content in the small intestinal epithelium was measured and immunoreactivity was examined using anti-mucin monoclonal antibodies HCM31 and PGM34.


RESULTS
Indomethacin caused punched out and linear ulcers located mostly along the mesenteric margin of the distal jejunum with sparing of the ileum. Histological examination showed sialomucin recognized by HCM31 increased on day 3 especially in the regenerating epithelium around the ulcer edge. Furthermore, the surface mucous gel layer displayed a multilaminated pattern, consisting of non-sulfated sialomucin-rich layers and sulfated mucin-rich layers, where both mucins had the common core protein, MUC2. Biochemical measurements also showed the total mucin content of the jejunum increased transiently and HCM31-positive mucin increased approximately 4 times greater than baseline on day 3, but no marked changes were observed in the ileum, with few ulcers observed.


CONCLUSIONS
Indomethacin administration causes quantitative and qualitative change in jejunal mucin. In particular, sialomucin plays an important role in regenerating epithelium during the healing process following indomethacin-induced mucosal damage.
Iwai
Tomohisa
T
Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
Ichikawa
Takafumi
T
Goso
Yukinobu
Y
Ikezawa
Tomoaki
T
Saegusa
Yoichi
Y
Okayasu
Isao
I
Saigenji
Katsunori
K
Ishihara
Kazuhiko
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000276:immunology; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D009077:Mucins / Q000187:drug effects / Q000276:immunology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D052116:Sialomucins / Q000378:metabolism; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D009077:Mucins; D052116:Sialomucins; D007213:Indomethacin