Effects of rebamipide on gastric cell damage by Helicobacter pylori-stimulated human neutrophils.
Helicobacter pylori stimulated human neutrophils to produce oxygen radicals as evidenced by the production of chemiluminescence in the presence of luminol. The capacity of H. pylori to produce oxygen radicals from neutrophils was much higher than that of Escherichia coli and Staphylococcus aureus and is almost as strong as that of PMA. Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid) suppressed the chemiluminescence produced by H. pylori-stimulated neutrophils and also suppressed the chemiluminescence produced by a cell-free xanthine/xanthine oxidase reaction with luminol. Thus, it is indicated that this drug has the action of scavenging oxygen radicals. Gastric mucosal cells labelled with a fluorescent dye were damaged by the incubation of the cells with neutrophils and H. pylori, and this damage was protected by rebamipide. The protection of cell damage was ascertained as a decrease in the release of fluorescent dye into the incubation medium and a reduction in the distortion of cell geometry. The data suggest that H. pylori induce human neutrophils to produce oxygen radicals which are responsible for gastric mucosal cell damage and that rebamipide removes the oxygen radicals produced from H. pylori-activated neutrophils and thus reduces the gastric mucosal cell damage. These effects may account for the ulcerogenesis action of H. pylori and for part of the mechanism of the anti-ulcer action of rebamipide.
Han
B G
BG
Department of Pharmacology, Seoul National University College of Medicine, Korea.
Kim
H S
HS
Rhee
K H
KH
Han
H S
HS
Chung
M H
MH
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016480:Helicobacter pylori; D006801:Humans; D009504:Neutrophils / Q000187:drug effects*; D010437:Peptic Ulcer / Q000188:drug therapy*; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D000897:Anti-Ulcer Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine