Selective cyclooxygenase-2 inhibitor induces gastric mucosal damage in adrenalectomized rats

We investigated gastric ulcerogenic properties of the selective COX-2 inhibitor in adrenalectomized rats. SC-560 (selective COX-1 inhibitor) or celecoxib (selective COX-2 inhibitor) was given to sham-operated and adrenalectomized rats, with or without corticosterone replacement 11 days after the surgery, and gastric lesions were estimated 8 h later. Neither SC-560 nor celecoxib alone induced any gross damage in the gastric mucosa in sham-operated rats. In adrenalectomized rats, however, celecoxib did provoke gross damage that was prevented by corticosterone pellets. Mucosal PGE2 content was increased 3-fold after adrenalectomy, and this response was prevented by both celecoxib and corticosterone pellets. The COX-2 mRNA was up-regulated in the stomach of adrenalectomized rats, but this expression was suppressed by corticosterone replacement. These results support our hypothesis that adrenalectomy increases gastric mucosal PGE2 due to COX-2 expression, and the selective COX-2 inhibitor produces gastric lesions by inhibiting the additional PGE2 production in adrenalectomized rats.