Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

Helicobacter pyloriDisrupts NADPH Oxidase Targeting in Human Neutrophils to Induce Extracellular Superoxide Release

“…The receptors and adhesins that modulate Hp phagocytosis have not been defined, and how these organisms evade phagocytic killing is unclear. At the same time, the results of several studies indicate that Hp can activate neutrophils in vitro (3)(4)(5)(6)(7)(8). Moreover, neutrophil density in vivo correlates directly with the ability of Hp to cause severe disease (9 -11), and the available data suggest that neutrophils and bacteria act in concert to induce gastric ulceration (8,10,12,13).…”

“…5A). Cell activation by HP-NAP and Hp(2-20) is sensitive to PTx and Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) acts via FPRL1 (34). Notably, the fMLP-triggered respiratory burst was efficiently blocked by PTx (4.5 Ϯ 7.8% of control (n ϭ 6)), but responses to Hp were unaffected (103 Ϯ 6% of control (n ϭ 6)).…”

“…Notably lacking is a direct measurement of the Hp-induced respiratory burst. Previous studies have used luminol chemiluminescence (CL) to assess PMN activation by Hp (3)(4)(5)(6)(7)(8). Although this assay is very sensitive, it detects oxidants generated in the presence of myeloperoxidase and as such cannot be used to measure NADPH oxidase activity (18).…”

Role of Rebamipide on Induction of Heat-Shock Proteins and Protection Against Reactive Oxygen Metabolite-Mediated Cell Damage in Cultured Gastric Mucosal Cells

“…These effects have been interpolated from its pharmacological action on prostaglandin synthesis in gastric epithelium. 6,7 Yamasaki et al 6 have reported that rebamipide increases gastric mucosal prostaglandin concentration and protects the mucosa from damage induced by the necrotizing agents. Rebamipide also has another distinctive pharmacological defense against gastric mucosal damages, that is, it may not only scavenge hydroxyl radicals, but also suppress active oxidant production by modulating the neutrophil activation process.…”

“…Rebamipide has two distinct pharmacological features, increasing endogenous prostaglandin and scavenging ROM. [6][7][8][9] An antiulcer effect of rebamipide was related to inhibition of the production of ROM by activated neutrophils. 9 However, the underlying mechanism by which rebamipide exerts its cytoprotective effect in the damaged stomach is not yet fully determined.…”