Nonsteroidal anti-inflammatory drug-induced acute gastric injury in Helicobacter pylori gastritis in Mongolian gerbils.

Abstract We examined the acute ulcerogenic effects of indomethacin and N -(2,cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS-398) on the gastric mucosa in Helicobacter pylori -infected Mongolian gerbils. H. pylori infection for 4 and 12 weeks caused moderate and severe gastritis, respectively, with cyclooxygenase-2 expression and an increase in prostaglandin E 2 production. In normal animals, gastric injury was caused by indomethacin, but not by NS-398. At 4 weeks infection, gastric lesions were synergistically aggravated by indomethacin, and NS-398 at high doses. However, at 12 weeks, the synergistic effects of indomethacin and NS-398 with H. pylori were not observed. Indomethacin and NS-398 at high doses inhibited prostaglandin E 2 production in both normal and the infected mucosa. NS-398 at low dose reduced only the H. pylori -increased prostaglandin production. These results suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically aggravate gastric lesions in moderate H. pylori gastritis, but not in severe gastritis. Cyclooxygenase-2 inhibition only might not induce acute gastric injury in H. pylori gastritis.