Acid-Independent Gastroprotective Effects of Lansoprazole in Experimental Mucosal Injury
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- Blandizzi, C., Natale, G., Gherardi, G. et al. Dig Dis Sci (1999) 44: 2039. doi:10.1023/A:1026626519534
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The protective effects of the proton pumpinhibitor lansoprazole on gastric mucosal damage inducedby ethanol-HCl or hemorrhagic shock were investigated inthe present study. The morphometric analysis of gastric histological sections revealed thatlansoprazole dosedependently reduced mucosal injuryevoked by ethanol-HCl (ED50 = 24.3μmol/kg) or hemorrhagic shock (ED50 = 38.9μmol/kg), these effects being associated with markedincrements of Alcian blue recovery from gastric boundmucus (ED50 = 31.4 μmol/kg and 27.6μmol/kg, respectively). In addition, lansoprazoleinhibited gastric acid secretion from pylorusligated rats(ED50 = 9.8 μmol/kg). Further experiments,performed on rats with ethanol-HCl-induced gastricinjury, indicated that the protective effects of lansoprazole were not modified by L-365,260,suramin, NG-nitro-L-arginine, or systemicablation of capsaicin-sensitive sensory nerves, whereasthey were partly blocked by indomethacin and fullyprevented by N-ethyl-maleimide. In addition, lansoprazoledid not modify somatostatin concentrations in gastricmucosa. The present results provide evidence thatlansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagicshock. According to the rank order of ED50values, these effects appear to depend mainly on theenhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is alsoproposed that an increased production of prostaglandins,as well as an increased availability of sulfhydrylcompounds at level of gastric mucosa may account for the gastroprotective effects oflansoprazole.