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Role of prostaglandin deficiency in pathogenetic mechanism of gastric lesions induced by indomethacin in rats

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Abstract

The present study was undertaken in rats using 2-deoxy-D-glucose (2DG) as a stimulator of gastric motility and a low dose of indomethacin as a prostaglandin (PG) synthesis inhibitor to investigate the roles of gastric motility and PG deficiency in the pathogenesis of indomethacin-induced gastric lesions. Subcutaneously administered indomethacin at 5 mg/kg did not induce any visible damage in the mucosa within 4 hr, but at 25 mg/kg produced linear hemorrhagic lesions along the long axis of the stomach. 2DG (100 mg/kg/hr), given intravenously, produced linear nonhemorrhagic lesions along the mucosal folds and, in the presence of 5 mg/kg of indomethacin, caused severe hemorrhagic lesions in the same areas of the stomach. Gastric motility was markedly enhanced by both indomethacin (25 mg/kg) and 2DG, while acid output and mucosal blood flow were increased only by the latter. Mucosal PGE 2 levels were significantly reduced by indomethacin (25 mg/kg) but not by 2DG. Indomethacin at 5 mg/kg alone had no or little effect on any parameter except PG levels, which were reduced to similar degrees as caused by 25 mg/kg of the agent. Time-course development of the lesions was closely associated with those changes in gastric motility after administration of indomethacin (25 mg/kg) and 2DG. These results suggest that the enhanced gastric motility is, by itself, sufficient to induce damage (nonhemorrhagic) in the mucosa and that a PG deficiency alone does not induce any damage but is required for further extension to hemorrhagic lesions of nonhemorrhagic ones that are initially induced by enhanced gastric motility.

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Authors and Affiliations

  1. Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, 607, Kyoto, Japan

    Megumu Okada MA, Hiromichi Niida MA, Koji Takeuchi PhD & Susumu Okabe PhD

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  1. Megumu Okada MA
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  2. Hiromichi Niida MA
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  3. Koji Takeuchi PhD
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  4. Susumu Okabe PhD
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Okada, M., Niida, H., Takeuchi, K. et al. Role of prostaglandin deficiency in pathogenetic mechanism of gastric lesions induced by indomethacin in rats. Digest Dis Sci 34, 694–702 (1989). https://doi.org/10.1007/BF01540340

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  • DOI: https://doi.org/10.1007/BF01540340

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