Abstract
Gastric lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs) are considered to involve multiple pathogenic elements, such as deficiency of prostaglandins (PGs), gastric hypermotility, neutrophil activation and luminal acid. The present study was performed to examine the effects of these elements, either alone or in combination, on the rat gastric mucosa and to investigate which element may be most closely associated with gastric ulcerogenic response to NSAID. The following treatments were employed to express various pathogenic elements: a low dose of indomethacin to cause PG deficiency; 2-deoxy-n -glucose (2DG) to induce gastric hypermotility and acid secretion; histamine to induce acid hypersecretion; and n-formyl-Met-Leu-Phe (fMLP) to elicit neutrophil activation. When rats which had been fasted for 18 h were subjected to each treatment alone and killed 4 h later, only 2DG caused slight macroscopic damage in the gastric mucosa. Indomethacin showed over 90% inhibition of the mucosal PG generation, and fMLP increased the myeloperoxidase activity to 4 times greater than normal values, yet neither of these treatments alone caused any damage in the stomach. The combined treatments of indomethacin with 2DG or histamine caused severe lesions in the stomach or the duodenum, respectively, whereas fMLP did not modify or potentiate the mucosal ulcerogenic propensity to other treatments. We conclude that (1) among various pathogenic components both gastric hypermotility and PG deficiency are crucial for induction of gross damage in the rat stomach; gastric hypermotility is by itself sufficient to induce mild damage in the mucosa, while PG deficiency is prerequisite for later extension of damage to severe lesions, and (2) the neutrophil activation alone is not ulcerogenic in the gastric mucosa or does not potentiate the ulcerogenic effect of other elements.
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© 1997 Springer Science+Business Media Dordrecht
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Takeuchi, K., Kato, S., Takehara, K., Asada, Y. (1997). Analyses of Pathogenic Elements Involved in Gastric Lesions Induced by Indomethacin in Rats. In: Mózsik, G., Nagy, L., Pár, A., Rainsford, K.D. (eds) Cell Injury and Protection in the Gastrointestinal Tract. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5392-8_2
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DOI: https://doi.org/10.1007/978-94-011-5392-8_2
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