Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.
The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity.
Suzuki
M
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
S
S
Mori
M
M
Kai
A
A
Suzuki
H
H
Fukumura
D
D
Suematsu
M
M
Tsuchiya
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology / Q000502:physiology*; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D016877:Oxidants / Q000009:adverse effects* / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D014510:Urease / Q000378:metabolism
D000897:Anti-Ulcer Agents; D016877:Oxidants; D015363:Quinolones; D014510:Urease; C052785:rebamipide; D000409:Alanine