Changes in the Mucus Barrier during Cisplatin-Induced Intestinal Mucositis in Rats

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.

Alterations in the small intestinal wall and motor function after repeated cisplatin in rat

“…Ki‐67 is widely used as a cell proliferation marker . Whereas some antineoplastic drugs, such as methotrexate, do not affect this early proliferation marker in the mucosa, cisplatin decreased proliferating cells in the few hours after its administration . However, we did not detect any significant change in this parameter, suggesting that mucosal proliferation was recovered 1 week after the last cisplatin administration.…”

“…Cisplatin causes profound gastrointestinal symptoms that in humans may occur even months to years after treatment finalization . These symptoms may be related to structural damage of the mucosa (which other antineoplastic drugs may also induce), although most published data refer to acute doses . Instead, we used lower doses, repeatedly administered, more adequate to mimic the clinical situation.…”

Detection of dietary plant-based small RNAs in animals

“…We hypothesize that the cisplatin experiments exemplify phenotypes that may occur during various disease states that cause "leaky gut"-type symptoms. Cisplatin does not exclusively damage cancer cells and has diverse side effects, including changes in the organization of the GI tract [9]. Our results suggest that altered or damaged guts resulting from illness and/ or therapeutic treatments could enhance dietary RNA uptake.…”

Gastroduodenal mucosal defense

“…Yamamoto et al reported that luminal mucin concentration within the GI tract was most markedly reduced three days after administration of cisplatin, returning to baseline by day eleven (Figure 2) [27]. IIjima et al reported that ten days of aspirin treatment significantly increased the rate of gastric mucus secretion with a concomitant and significant decrease in the gastric acid secretion rate /mucus secretion rate.…”

“…This demonstrates the nadir of gastric mucus on day 3 followed by full recover on day 11. Adapted from [27]…”