Nonsteroidal anti-inflammatory drug-induced acute gastric injury in Helicobacter pylori gastritis in Mongolian gerbils.
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.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, 607-8414, Kyoto, Japan. takahasi@mb.kyoto-phu.ac.jp
Fujita
T
T
Yamamoto
A
A
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005756:Gastritis / Q000473:pathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology*; D016480:Helicobacter pylori; D007213:Indomethacin / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism; D009578:Nitrobenzenes / Q000633:toxicity; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013449:Sulfonamides / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin