Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors, acetohydroxamic acid and flurofamide, in Mongolian gerbils

Urease has been suggested to be essential for colonization and pathogenesis of Helicobacter pylori infection. In the present study, we evaluated the e ffects of urease inhibitors [acetohydroxamic acid (AHA) and flurofamide (FF A)] on H. pylori-induced gastritis in Mongolian gerbils. Animals were orall y inoculated with H. pylori, and given urease inhibitors in their diet thro ughout the experimental period of six weeks or four weeks, starting from tw o weeks after H. pylori inoculation. With the administration of ARA at dose s of 100, 500, and 2500 ppm throughout the experimental period, H. pylori-i nduced gastritis in animals was decreased in a dose-dependent manner, signi ficantly so at 2500 ppm. Suppression of gastric lesions was also evident in animals administered 2500 ppm AHA after the H. pylori infection. Bacterial infection rates were reduced to 40-50% of the control value of 100%, by th e highest dose of AHA. The potent urease inhibitor, FFA, also caused marked amelioration of H. pylori-associated gastritis on administration at 100 pp m throughout the six-week experimental period or for four weeks after H. py lori infection. Animals treated with FFA had few visible gastric lesions, a nd the proportion infected with H. pylori was reduced to less than 10%. Sin ce antibiotic-resistant strains of H. pylori have become a serious problem, nonantibiotic, urease inhibitors, may be very useful to control H. pylori- associated gastroduodenal disease. (C) 2001 Academic Press.