Influence of H2-receptor antagonists on intestinal mucositis induced by 5-fluorouracil in rats

AIM: Although histamine (H2) receptor antagonists appear clinically beneficial; their effects on chemotherapyinduced mucositis remain poorly understood. Therefore, we compared the influences of cimetidine, famotidine, and lafutidine on intestinal mucositis induced by 5-fluorouracil (5-FU) in rats. Simultaneously, we assessed whether the antitumor efficacy was influenced by these treatments for mucositis. METHODS: Rats were divided into five groups. The first group (control) was orally administered 0.5% carboxymethylcellulose once daily for 5 or 7 days. The second, third, fourth, and fifth groups were treated with 5FU (30 or 50 mg/kg), 5-FU plus cimetidine (100 mg/kg), 5-FU plus famotidine (5 mg/kg), and 5-FU plus lafutidine (30 mg/kg), respectively. We compared the levels of antitumor activity and mucosal damage among these groups. Furthermore, the possible participation of capsaicin-sensitive afferent neurons was investigated. RESULTS: 5-FU was shown to reduce weight gain and intestinal mucin accumulation. Oral administration of the H2-receptor antagonists had no effect on the antitumor activity of 5-FU. Lafutidine, but neither cimetidine nor famotidine, prevented the 5-FU-induced side effects, including reduction of bodyweight gain, mucosal damage, and decrease in mucin content. These beneficial effects disappeared after capsaicin-sensitive afferent neurons were ablated. CONCLUSION: Second-generation H2-receptor antagonists may lead to a more effective prevention of chemotherapy-induced intestinal mucositis.