Interaction between NSAIDs and steroid in rat stomach: Safety of nimesulide as a preferential COX-2 inhibitor in the stomach

• Published in: Digestive diseases and sciences Vol. 45; no. 7; pp. 1366 - 1375
• Main Authors: KATAOKA, H, HORIE, Y, KOYAMA, R, NAKATSUGI, S, FURUKAWA, M
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-07-2000; Springer Nature B.V
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; DNA - biosynthesis; Drug Interactions; Drug Synergism; Drug toxicity and drugs side effects treatment; Gastric Mucosa - drug effects; Gastric Mucosa - enzymology; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastrointestinal Motility - drug effects; Indomethacin - pharmacology; Isoenzymes - antagonists & inhibitors; Male; Medical sciences; Membrane Proteins; Peroxidase - metabolism; Pharmacology. Drug treatments; Prednisolone - pharmacology; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Stomach - drug effects; Stomach Ulcer - chemically induced; Sulfonamides - pharmacology; Toxicity: digestive system; Corticosteroid; Stomach; Drug combination; Rat; Cyclooxygenase 2; Rodentia; Cytotoxicity; Synergism; Non steroidal antiinflammatory agent; Vertebrata; Experimental disease; Mammalia; Animal; Digestive diseases; Nimesulide; Safety; Mechanism of action; Gastric disease
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/a:1005560104847

The relative risk of development of peptic ulcer with the use of nonsteroidal antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs are administered in combination with steroids. We investigated the ulcerogenic potential of a combination of NSAIDs and steroids in rats and the underlying pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the severity of the lesions markedly increased with concomitant administration of prednisolone. However, nimesulide, even in excessive doses, did not produce any gastric lesions, regardless of concomitant administration with prednisolone. Furthermore, we showed that the ulcerogenic potential of indomethacin administered in combination with prednisolone may be related to the induction of physiological changes, such as endogenous prostaglandin deficiency, an increase in neutrophil activation, and gastric hypermotility, by indomethacin and alteration of normal epithelial renewal by the steroid. These results suggest that the ulcerogenic potential of preferential a COX-1 inhibitor increases following concomitant administration with a steroid, whereas, nimesulide, a preferential COX-2 inhibitor, is nonulcerogenic, even when administered concomitantly with a steroid, and is therefore a clinically useful antiinflammatory agent.