Abstract
Aim. 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. Conclusion. Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells.
Highlights
Gastrointestinal (GI) mucositis, a frequent complication of antineoplastic chemotherapy, can reduce treatment effectiveness because it leads to dose reductions, increased healthcare costs, and an impaired quality of life [1, 2]
Several experimental studies have investigated the mechanisms of small-intestinal-mucosal injury induced by 5-FU [10, 11], and we have recently reported significant changes in the mucus barrier of the rat during 5-FU-induced GI mucositis [12]
We found that intravenous injection of cisplatin in a single dose of 6 mg/kg caused GI mucosal damage altered the GI
Summary
Gastrointestinal (GI) mucositis, a frequent complication of antineoplastic chemotherapy, can reduce treatment effectiveness because it leads to dose reductions, increased healthcare costs, and an impaired quality of life [1, 2]. Some of the newer H2-receptor antagonists (so-called second-generation H2receptor antagonists) have been frequently used in Japan. These agents have a unique component structurally differing from conventional H2-receptor antagonists and promote gastric mucosal defense mechanisms, including mucus secretion [7]. Medical therapy has improved the management of symptoms in patients with chemotherapy-induced mucositis [3,4,5,6], their effects on mucosal defense mechanisms remain poorly understood. Cisplatin is well known to be associated with renal toxicity [13, 14], but there is a dearth of information about its effects on the GI mucosa
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