Changes in the mucus barrier during cisplatin-induced intestinal mucositis in rats.
OBJECTIVE
Gastrointestinal mucositis is a frequent complication of antineoplastic chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms remain poorly understood. We studied the effects of cisplatin on mucin, one of the principal defense factors of the gastrointestinal mucosa, and evaluated the efficacy of two different types of H2-receptor antagonists against cisplatin-induced mucositis.


METHODS
Cisplatin (6 mg/kg) was administered intravenously to rats (day 0). The rats were sacrificed 1, 3, 7, and 11 days after treatment, and their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg) or lafutidine (30 mg/kg) was given orally once daily on days 0, 1, and 2. Histological and biochemical findings were compared among the groups to assess effects on cisplatin-induced injury.


RESULTS
Cisplatin significantly altered the immunoreactivity and content of mucin in the small intestinal mucosa, especially in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and attenuated decreased mucin accumulation.


CONCLUSIONS
Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells.
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Hajime
H
Yamamoto
Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
Kazuhiko
K
Ishihara
Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
Yuko
Y
Takeda
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Wasaburo
W
Koizumi
Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
Takafumi
T
Ichikawa
D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology*; D010880:Piperidines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats
D000081:Acetamides; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D002945:Cisplatin