Acid-independent gastroprotective effects of lansoprazole in experimental mucosal injury

The protective effects of the proton pump inhibitor lansoprazole on gastric mucosal damage induced by ethanol-HCl or hemorrhagic shock were investigat ed in the present study. The morphometric analysis of gastric histological sections revealed that lansoprazole dose-dependently reduced mucosal injury evoked by ethanol-HCl (ED50 = 24.3 mu mol/kg) or hemorrhagic shock (ED50 3 8.9 mu mol/kg), these effects being associated with marked increments of Al cian blue recovery from gastric bound mucus (ED50 = 31.4 mu mol/kg and 27.6 mu mol/kg, respectively). In addition, lansoprazole inhibited gastric acid secretion from pylorus-ligated rats (ED50 = 9.8 mu mol/kg). Further experi ments, performed on rats with ethanol-HCl-induced gastric injury, indicated that the protective effects of lansoprazole were not modified by L-365,260 , suramin, NG-nitro-L-arginine, or systemic ablation of capsaicin sensitive sensory nerves, whereas they were partly blocked by indomethacin and fully prevented by N-ethyl-maleimide. In addition, lansoprazole did not modify s omatostatin concentrations in gastric mucosa. The present results provide e vidence that lansoprazole prevents the necrotic damage of gastric mucosa in duced by ethanol-HCl or hemorrhagic shock. According to the rank order of E D50 values, these effects appear to depend mainly on the enhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It i s also proposed that an increased production of prostaglandins, as well as an increased availability of sulfhydryl compounds at level of gastric mucos a may account for the gastroprotective effects of lansoprazole.