Gastroprotective effect of bezafibrate, a peroxisome proliferator activated receptor α agonist and its mechanism in a rat model of aspirin-induced gastric ulcer

SummaryBackgroundThe aim of the present study was to demonstrate the antiulcer activity and mechanism of bezafibrate in a rat model of aspirin-induced gastric ulcer.MethodsWe used an aspirin-induced gastric ulcer model. Bezafibrate was administered orally in graded doses (10 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) to detect the best effective antiulcer dose of bezafibrate. The parameters measured were: ulcer index, histopathological scoring of gastric ulcer, gastric juice analysis, gastric mucosal lipid peroxidation parameters, estimation of NO metabolite in blood, mRNA expression of inducible NO synthase iNOS and constitutive NO synthase (cNOS) in gastric mucosa, and gastric mucosal DNA fragmentation.ResultsThe dose-dependent antiulcer activity of bezafibrate was shown by the ulcer index and histopathological score. Bezafibrate (100 mg/kg) significantly reduced total acidity, free acidity, and pepsin activity, and increased total hexoses and total proteins. Bezafibrate (100 mg/kg) also significantly reduced lipid peroxidation, inhibited iNOS expression, preserved cNOS expression, and inhibited DNA fragmentation.ConclusionBezafibrate can decrease aspirin-induced gastric mucosal injury via reducing lipid peroxidation, inhibiting iNOS expression, preserving cNOS expression, and decreasing DNA fragmentation.