IN-VITRO STUDIES INDICATING ANTIOXIDATIVE PROPERTIES OF REBAMIPIDE

Rebamipide is the first anti-gastric ulcer and antigastritis drug that not only increases endogenous prostaglandin in gastric mucosa but als o scavenges oxygen-derived free radicals and inhibits their production . In the present paper, we have reviewed the antioxidative and antiinf lammatory properties of rebamipide mainly demonstrated by in vitro stu dies. The study, using the electron paramagnetic resonance (EPR) spin trapping technique, showed that superoxide production was inhibited by rebamipide when isolated human neutrophils were stimulated with opson ized zymosan or Helicobacter pylori water extract in a dose-dependent manner. Chemiluminescence generated from neutrophils activated by H. p ylori or formyl-methionyl-leucyl-phenylalanine was also decreased by t he treatment with rebamipide. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cell s as well as the CD18 expression on neutrophils induced by H. pylori w ater extract. The EPR study also demonstrated the direct hydroxyl radi cal scavenging activity of rebamipide, and a kinetic study showed that the second-order rate constant for the reaction between rebamipide an d hydroxyl radical was 2.24 x 10(10) M-1/s(-1). The inhibitory effect of rebamipide on lipid peroxidation induced by a free radical initiato r was also demonstrated by the in vitro system using rat gastric mucos al homogenates. These data indicate that rebamipide offers a potential for protection against reactive oxygen- and activated neutrophil-asso ciated gastric mucosal injury by scavenging hydroxyl radical and inhib iting neutrophil activation or lipid peroxidation.