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

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Abstract

Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 μmol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 μmol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.

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Abbreviations

CD:

Crohn’s disease

CFU:

colony-forming unit

CMC:

carboxymethylcellulose

COX:

cyclooxygenase

HTAB:

hexadecyl trimethyl ammonium bromide

IBD:

inflammatory bowel disease

MDA:

malondialdheyde

MPO:

myeloperoxidase

NSAID:

nonsteroidal anti-inflammatory drug

PG:

prostaglandin

PPI:

proton pump inhibitor

TBARS:

thiobarbituric acid reactive substances

TSA:

tryptone soya agar

UC:

ulcerative colitis

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Acknowledgements

This work was supported by a grant from the Italian Ministry of Education, University and Research.

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Authors and Affiliations

  1. Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Via Volturno 39, 43100, Parma, Italy

    Cristina Pozzoli, Alessandro Menozzi, Daniela Grandi, Elvira Solenghi & Gabriella Coruzzi

  2. Department of Animal Health, University of Parma, Via Del Taglio 8, 43100, Parma, Italy

    Maria C. Ossiprandi, Chiara Zullian & Simone Bertini

  3. Department of Clinical Sciences, Via Gramsci 14, 43100, Parma, Italy

    Giulia M. Cavestro

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  1. Cristina Pozzoli
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  2. Alessandro Menozzi
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  4. Elvira Solenghi
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  5. Maria C. Ossiprandi
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  9. Gabriella Coruzzi
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Correspondence to Gabriella Coruzzi.

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Pozzoli, C., Menozzi, A., Grandi, D. et al. Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine. Naunyn-Schmied Arch Pharmacol 374, 283–291 (2007). https://doi.org/10.1007/s00210-006-0121-y

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