Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis.
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.
Saegusa
Yoichi
Y
Department of Internal Medicine, Kitasato University Graduate School of Medicine, Sagamihara, Kanagawa, Japan.
Ichikawa
Takafumi
T
Iwai
Tomohisa
T
Goso
Yukinobu
Y
Ikezawa
Tomoaki
T
Nakano
Motoko
M
Shikama
Nobuaki
N
Saigenji
Katsunori
K
Ishihara
Kazuhiko
K
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
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