Experimental study of the safety of the selective COX‐2 inhibitor, celecoxib, for gastric mucosa

Abstract

OBJECTIVE:  To compare the gastric mucosal damage induced by a COX-2 inhibitor, celecoxib, and a conventional NSAID, indomethacin. METHODS:  A rat model of NSAID-induced gastric mucosal damage was prepared for indomethacin and celecoxib separately (n = 8). After gastric damage was induced by 100% ethanol, celecoxib was administered by gastric gavage (n = 8). Gastric mucosal concentrations of 6-keto-PGF1α and TXB2 and the lesion index (LI) were measured. Morphological changes of the gastric mucosa were assessed under light and scanning electron microscopy. RESULTS:  Indomethacin caused marked gastric damage (LI: 13.38 ± 2.06) and significant reduction of the concentrations of 6-keto-PGF1α and TXB2 (P < 0.01), Celecoxib did not produce necrotic injuries on healthy gastric mucosa (LI: 0), but the mucosal injuries previously induced by ethanol worsened after its administration (LI: 37.19 ± 3.34 vs 19.90 ± 2.28, P < 0.01). CONCLUSIONS:  Inhibition of COX-1 is the major mechanism of NSAIDs in producing gastric mucosal damage. As a selective COX-2 inhibitor, celecoxib does not produce toxic injuries of the healthy gastric mucosa, and is thus safer than conventional NSAID. However, when administered in the presence of an altered gastric mucosa, gastric injuries were worsened.