Role of lipid peroxidation in protection of rats by rebamipide against gastric mucosal lesions induced by stress plus indomethacin

The roles of lipid peroxidation and prostaglandins (PGs) in the protective effect of rebamipide against gastric lesions in rats induced by stress plus indomethacin were investigated. Lesions of the gastric mucosa were induced within 3 h by restraint in water (23°C) plus intraperitoneal injection of indomethacin (20 mg/kg) but not by either of these treatments alone. Lipid peroxidation, measured as TBA reactive substances, was increased by stress + indomethacin treatment and the increase in TBA reactive substances was closely related to the lesion score (P < 0.01). This treatment also reduced the release of PGE2 from the gastric mucosa, the reduction being related with the lesion score (P < 0.01). Teprenone, an inducer of endogenous PGE2, did not inhibit the induction of gastric lesions by stress + indomethacin. Rebamipide injected subcutaneously dose-dependently inhibited the induction of lesions at doses of 3–30 mg/kg. At a dose of 30 mg/kg, it inhibited the increase of TBA reactants in the gastric mucosa, but did not completely restore PGE2 release. In the rebamipide-treated group, a significant correlation (P < 0.01) was found between the lesion score and the changes in TBA reactants, but not the PG levels. These results indicate that inhibition of lipid peroxidation may be an important factor in the protective effect of rebamipide against gastric lesions in rats induced by stress + indomethacin.