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Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin

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Abstract

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 µmol/kg; indomethacin 100 µmol/kg; and esomeprazole 10, 30, or 60 µmol/kg plus indomethacin 100 µmol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10–60 µmol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.

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Acknowledgments

We thank Dr. Elena Pigoli for reading the manuscript and for her helpful comments. This study was funded in full by a research grant from AstraZeneca.

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The authors state there is no conflict of interest.

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Authors and Affiliations

  1. Department of Physiological and Pharmacological Sciences, University of Pavia, Piazza Botta 11, 27100, Pavia, Italy

    O. Pastoris, M. Verri, F. Boschi, B. Balestra & M. Tonini

  2. Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126, Pisa, Italy

    O. Kastsiuchenka & G. Natale

  3. Division of Gastroenterology ‘L. Sacco’ University Hospital, University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy

    F. Pace

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  1. O. Pastoris
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  2. M. Verri
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  7. M. Tonini
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Correspondence to M. Tonini.

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Pastoris, O., Verri, M., Boschi, F. et al. Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin. Naunyn-Schmied Arch Pharmacol 378, 421–429 (2008). https://doi.org/10.1007/s00210-008-0314-7

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  • DOI: https://doi.org/10.1007/s00210-008-0314-7

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