Both selective COX-1 and COX-2 inhibitors aggravate gastric damage induced in rats by 2-deoxy-D-glucose: Relation to gastric hypermotility and COX-2 expression

Background/Aim: 2-Deoxy-D-glucose (2DG), despite causing gastric hypermotility via vagal stimulation, does not by itself induce damage in the stomach but produces gross lesions under prostaglandin (PG) deficiency induced by non-ulcerogenic dose of indomethacin. In this study, we examined the roles PG and cyclo-oxygenase (COX) isozymes play in the gastric ulcerogenic effect of 2DG in the rat stomach under PG deficiency caused by indomethacin. Methods: The animals were given 2DG i.v. (200 mg/kg as a bolus injection followed by an infusion at 100 mg/kg), and the mucosa was examined for lesions 8 h later. SC-560 or/and rofecoxib was given p.o. 1 h before 2DG treatment. Results: 2DG alone caused slight damage in the stomach despite causing acid hypersecretion and hypermotility. Neither SC-560 nor rofecoxib alone caused any damage in the stomach, yet these agents significantly aggravated 2DG-induced gastric lesions; the severity of damage was much greater when SC-560 was given together with 2DG. SC-560, but not rofecoxib, enhanced both acid secretion and gastric motility in response to 2DG, with a decrease in mucosal PGE₂ content. Expression of COX-2 was up-regulated in the stomach as early as 2 h after 2DG treatment, and the PGE₂ content was increased when determined 6 h later, in a COX-2-dependent/rofecoxib-sensitive manner. Both the expression of COX-2 and gastric hypermotility during 2DG treatment were inhibited by prior administration of atropine but not omeprazole, although 2DG-induced gastric lesions were prevented by both agents. Conclusion: These results suggest that potentiation by indomethacin of 2DG-induced gastric lesions is related to inhibition of both COX-1 and COX-2, and that 2DG up-regulates COX-2 in the gastric mucosa, the event occurring in association with gastric hypermotility and contributing to suppression of later extension of the damage.