Role of mucus reduction and luminal acid elevation in increased susceptibility of stomach to nonsteroidal antiinflammatory drug-induced injury in arthritic rats.
We investigated the role of gastric mucus and acid secretion in the increase of nonsteroidal antiinflammatory drug-induced gastric lesions in adjuvant-induced arthritic rats. Both aspirin- and indomethacin-induced gastric injury were remarkably worsened in the arthritic rats. In the arthritic rats, the amounts of mucus glycoprotein in both the mucosa and adherent gel layer were respectively decreased to 70% and 34% of those in normal rats, while gastric acid secretion was augmented to 1.5-fold. The gastroprotective antiulcer agent ecabet sodium, which increased the mucus content in the gel layer but did not affect the luminal acid contents, prevented the increase of both lesions induced by aspirin and indomethacin. Cimetidine also inhibited the formation of aspirin- and indomethacin-induced damage as well as the acid secretion in the arthritic rats. In conclusion, an imbalance between gastric defensive and aggressive systems due to the loss of adherent mucus glycoprotein and the elevation of the luminal acid contents seems to account for the increased susceptibility of the lesion-inducing properties of nonsteroidal antiinflammatory drugs in arthritic rats.
Okuyama
K
K
Discovery Research Laboratory, Tanabe Seiyaku Co Ltd, Toda-shi, Saitama, Japan.
Jinbo
M
M
Saito
N
N
Igarashi
S
S
Narita
H
H
Kinoshita
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology*; D001241:Aspirin / Q000633:toxicity; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000633:toxicity; D009093:Mucus / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin