Rebamipide Reduces Recurrence of Experimental Gastric Ulcers: Role of Free Radicals and Neutrophils

Abstract

Mucosal inflammation is a crucial factor for the recurrence of peptic ulcer. In this study, we examined the effect of rebamipide on neutrophils infiltration, lipid peroxidation, and antioxidative enzyme activities in the recurrence of experimental gastric ulcer. Ulcer recurrence was examined at 60, 100, and 140 days after production of acetic acid-induced gastric ulcers in rats. Gastric neutrophil infiltration, lipid peroxidation, and antioxidative enzyme activities were determined by analyses of myeloperoxidase (MPO) activity, thiobarbituric acid reactive substance (TBARS) levels, and glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities in the ulcer region, respectively. The effect of rebamipide, an antigastric-ulcer agent, on ulcer recurrence was assessed following oral administration at 60 mg/kg/day from day 20. In the control and rebamipide groups, gastric ulcer indices were reduced on day 100 compared with day 60; however, increases were observed on day 140, indicating ulcer recurrence. In the rebamipide group, the ulcer index was smaller than in the control group at each time point and the effect was significant on day 140. Although marked elevation of MPO activities was observed in the control group during the experiment, no significant elevations were seen in the rebamipide group on days 100 and 140. TBARS levels were significantly elevated in the control group on day 140, but not in the rebamipide group. Rebamipide suppressed the decrease in GSHpx activity on day 60. These results suggest that lipid peroxidation of gastric tissue mediated by free radicals from neutrophils is responsible for the recurrence of acetic acid-induced gastric ulcers in rats, and that the elimination of free radicals by rebamipide may contribute to the reduction of severity in ulcer recurrence.

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

“…Among them, rebamipide suppresses inflammatory cell infiltration and the generation of free radicals, exhibits radical-scavenging action, and exerts a potent anti-inflammatory effect (Ogino et al, 1992;Sakurai et al, 2005). Indeed, this agent significantly reduced the severity of antral lesions produced by indomethacin plus paroxetine, together with the suppression of increased MPO activity as well as the restoration of decreased SOD activity and GSH content.…”

Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2

“…For these studies, the drug was suspended in 0.2% methylcellulose-saline solution (at a level of 20 mg drug/ml). For treatments, this suspension was then diluted and given via oral gavage at doses of 60 mg/kg/ day (Sakurai et al 2005) or 100 mg/kg/day (Diao et al 2012). Controls received corn oil and 0.2% methylcellulose-saline solution by gavage.…”

Antioxidant Activities of Agrimonia pilosa Ledeb: In Vitro Comparative Activities of Its Different Fractions

“…High levels of free radicals or active oxygen species create oxidative stress (Ordonez et al, 2006). Although normal cells possess antioxidant defense systems against ROS, the continuous accumulation of damage to the cells induces diseases such as gastric ulcers (Sakurai et al, 2005), colon cancer (Babbs, 1990), and hemolytic anemia (Jain and Hochstein, 1979). Human bodies are protected from oxidative stress by an efficient defense system, however, its capacity is affected by age, diet, and health status of the individual (Chun et al, 2003).…”