Saegusa Yoichi, Ichikawa Takafumi, Iwai Tomohisa, Goso Yukinobu, Ikezawa Tomoaki, Nakano Motoko, Shikama Nobuaki, Saigenji Katsunori, Ishihara Kazuhiko
Department of Internal Medicine, Kitasato University Graduate School of Medicine, Sagamihara, Kanagawa, Japan.
Scand J Gastroenterol. 2008;43(5):531-7. doi: 10.1080/00365520701811693.
Acid antisecretory agents are used for the prophylaxis of cancer chemotherapy (CT)-induced gastrointestinal (GI) mucositis. Although these drugs seem to be clinically beneficial, data on their effects on the GI mucosal defense during CT treatment are scant. The objective of this study was to compare the effects of omeprazole, lansoprazole, and lafutidine on mucin, a major mucus component, during 5-fluorouracil (5-FU) treatment, as a CT regimen.
Rats, weighing approximately 230 g, were divided into five groups. The control group was administered 0.5% carboxymethylcellulose orally once daily for 5 days. The second, third, fourth, and fifth groups were treated with 5-FU (50 mg/kg), 5-FU plus omeprazole (10 mg/kg), 5-FU plus lansoprazole (10 mg/kg), and 5-FU plus lafutidine (30 mg/kg) in the same way, respectively. The rats were sacrificed on the sixth day, and their stomachs and small intestines were removed. Using anti-mucin monoclonal antibodies, we compared the immunoreactivity in different areas of the rats' GI tracts as well as the mucin content.
Body-weight decreased in rats in the 5-FU group. Lafutidine, but neither omeprazole nor lansoprazole, inhibited the 5-FU-induced weight loss. Mucosal damage and reduced mucin content in stomach and small intestine were observed in rats receiving 5-FU alone. In the stomach, all antisecretory drugs caused the protective effects against 5-FU-induced mucosal injury and alleviation of the decreased mucin accumulation. In the jejunum and ileum, lafutidine, but neither omeprazole nor lansoprazole, ameliorated the 5-FU-induced mucosal damage and decreased mucin accumulation.
Lafutidine could offer the possibility of more effective prevention of CT-induced mucositis through the activation of GI mucus cells.
酸分泌抑制剂用于预防癌症化疗（CT）引起的胃肠道（GI）粘膜炎。尽管这些药物似乎具有临床益处，但关于它们在CT治疗期间对GI粘膜防御作用的数据却很少。本研究的目的是比较奥美拉唑、兰索拉唑和法莫替丁在作为CT方案的5-氟尿嘧啶（5-FU）治疗期间对粘蛋白（一种主要的粘液成分）的影响。
将体重约230g的大鼠分为五组。对照组每天口服一次0.5%羧甲基纤维素，持续5天。第二、第三、第四和第五组分别以相同方式用5-FU（50mg/kg）、5-FU加奥美拉唑（10mg/kg）、5-FU加兰索拉唑（10mg/kg）和5-FU加法莫替丁（30mg/kg）治疗。在第六天处死大鼠，取出它们的胃和小肠。使用抗粘蛋白单克隆抗体，我们比较了大鼠胃肠道不同区域的免疫反应性以及粘蛋白含量。
5-FU组大鼠体重下降。法莫替丁可抑制5-FU引起的体重减轻，而奥美拉唑和兰索拉唑则不能。单独接受5-FU治疗的大鼠出现胃和小肠粘膜损伤以及粘蛋白含量降低。在胃中，所有抗分泌药物均对5-FU引起的粘膜损伤具有保护作用，并减轻了粘蛋白积累的减少。在空肠和回肠中，法莫替丁可改善5-FU引起的粘膜损伤并减少粘蛋白积累，而奥美拉唑和兰索拉唑则不能。
法莫替丁可能通过激活GI粘液细胞更有效地预防CT引起的粘膜炎。
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