Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine

Proton pump inhibitors (PPIs) have been shownto be effective in preventing gastric and duodenal ulcers inhigh-risk patients taking nonsteroidal anti-inflammatorydrugs (NSAIDs); by contrast, scarce information is availableconcerning the effects of PPIs on intestinal damageinduced by NSAIDs in humans or in experimental animals.We examined the effects of lansoprazole and omeprazole onthe intestinal injury induced by indomethacin in theconscious rat. PPIs were administered by the intragastricroute at 30, 60 and 90 μmol/kg, 12 h and 30 min before and6 h after indomethacin treatment. The effects of omeprazoleand lansoprazole were evaluated on: (1) macroscopic andhistologic damage; (2) mucosal polymorphonuclear cellinfiltration; (3) oxidative tissue damage and (4) bacterialtranslocation from lumen into the intestinal mucosa.Lansoprazole and omeprazole (at 90 μmol/kg) significantlydecreased (P<0.01) the macroscopic and histologic damageinduced by indomethacin in the rat small intestine.Furthermore, both drugs greatly reduced (P<0.01) theassociated increases in myeloperoxidase levels and lipidperoxidation induced by indomethacin, whereas they onlymoderately affected (P<0.05) the translocation of enterobacteriafrom lumen into the intestinal mucosa. These datademonstrate that omeprazole and lansoprazole can protectthe small intestine from the damage induced by indomethacinin the conscious rat. The intestinal protection, possiblyrelated to antioxidant and anti-inflammatory properties ofthese drugs, may suggest new therapeutic uses of PPIs inintestinal inflammatory diseases.