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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Matteo Fornai, Luca Antonioli, Rocchina Colucci, Carolina Pellegrini, Giulio Giustarini, Lara Testai, Alma Martelli, Antuela Matarangasi, Gianfranco Natale, Vincenzo Calderone, Marco Tuccori, Carmelo Scarpignato and Corrado Blandizzi
Journal of Pharmacology and Experimental Therapeutics January 2014, 348 (1) 86-95; DOI: https://doi.org/10.1124/jpet.113.207118
Matteo Fornai
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Luca Antonioli
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Rocchina Colucci
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Carolina Pellegrini
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Giulio Giustarini
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Lara Testai
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Alma Martelli
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Antuela Matarangasi
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Gianfranco Natale
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Vincenzo Calderone
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Marco Tuccori
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Carmelo Scarpignato
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Corrado Blandizzi
Department of Clinical and Experimental Medicine (M.F., L.A., R.C., C.P., G.G., M.T., C.B.), Department of Pharmacy (L.T., A.Mar., V.C.), Department of Translational Research and New Technologies in Medicine and Surgery (A.Mat., G.N.), University of Pisa, Pisa, Italy; Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy (C.S.)
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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal damage, but the underlying mechanisms remain poorly understood. The present study investigated the effects of celecoxib, etoricoxib, indomethacin, and diclofenac on small bowel integrity in rats. Male rats were treated orally with test drugs for 14 days. Animals were processed for assessment of blood hemoglobin levels and hepatic mitochondrial functions, microscopic evaluation of small intestinal damage, Western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2) expression, and assay of malondialdehyde (MDA), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) levels in small intestine. Indomethacin and diclofenac decreased blood hemoglobin levels, whereas etoricoxib and celecoxib were without effects. Celecoxib caused a lower degree of intestinal damage in comparison with the other test drugs. Indomethacin and diclofenac, but not etoricoxib or celecoxib, reduced intestinal PGE2 levels. Test drugs did not modify intestinal COX-1 expression, although they enhanced COX-2, with the exception of celecoxib, which downregulated COX-2. Indomethacin, diclofenac, and etoricoxib altered mitochondrial respiratory parameters, although celecoxib was without effects. Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters, whereas in the ileum, etoricoxib, but not celecoxib, increased both MDA and MPO levels. These findings suggest that nonselective NSAIDs and etoricoxib can induce enteropathy through a topic action, whereas celecoxib lacks relevant detrimental actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs and the related effects on prostaglandin production do not appear to play a major role in the pathogenesis of enteropathy.

Footnotes

    • Received July 1, 2013.
    • Accepted October 17, 2013.
  • dx.doi.org/10.1124/jpet.113.207118.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 348 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 348, Issue 1
1 Jan 2014
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

NSAIDs and Intestinal Damage

Matteo Fornai, Luca Antonioli, Rocchina Colucci, Carolina Pellegrini, Giulio Giustarini, Lara Testai, Alma Martelli, Antuela Matarangasi, Gianfranco Natale, Vincenzo Calderone, Marco Tuccori, Carmelo Scarpignato and Corrado Blandizzi
Journal of Pharmacology and Experimental Therapeutics January 1, 2014, 348 (1) 86-95; DOI: https://doi.org/10.1124/jpet.113.207118

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

NSAIDs and Intestinal Damage

Matteo Fornai, Luca Antonioli, Rocchina Colucci, Carolina Pellegrini, Giulio Giustarini, Lara Testai, Alma Martelli, Antuela Matarangasi, Gianfranco Natale, Vincenzo Calderone, Marco Tuccori, Carmelo Scarpignato and Corrado Blandizzi
Journal of Pharmacology and Experimental Therapeutics January 1, 2014, 348 (1) 86-95; DOI: https://doi.org/10.1124/jpet.113.207118
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