title: Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Lafutidine could offer the possibility of more effective prevention of CT-induced mucositis through the activation of GI mucus cells.
authors.affiliation: Department of Internal Medicine, Kitasato University Graduate School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Iwai
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Goso
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikezawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Nakano
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikama
authors.forename: Katsunori
authors.initials: K
authors.lastname: Saigenji
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishihara
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D005472:Fluorouracil / Q000633:toxicity*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D064747:Lansoprazole; D008297:Male; D009077:Mucins / Q000032:analysis; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009853:Omeprazole / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000081:Acetamides; D000897:Anti-Ulcer Agents; D000964:Antimetabolites, Antineoplastic; D009077:Mucins; D010880:Piperidines; D011725:Pyridines; D064747:Lansoprazole; C076948:lafutidine; D009853:Omeprazole; D005472:Fluorouracil