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 effects of urease inhibitors [acetohydroxamic acid (AHA) and flurofamide (FFA)] on H. pylori-induced gastritis in Mongolian gerbils. Animals were orally inoculated with H. pylori, and given urease inhibitors in their diet throughout the experimental period of six weeks or four weeks, starting from two weeks after H. pylori inoculation. With the administration of AHA at doses of 100, 500, and 2500 ppm throughout the experimental period, H. pylori-induced gastritis in animals was decreased in a dose-dependent manner, significantly 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 the highest dose of AHA. The potent urease inhibitor, FFA, also caused marked amelioration of H. pylori-associated gastritis on administration at 100 ppm throughout the six-week experimental period or for four weeks after H. pylori infection. Animals treated with FFA had few visible gastric lesions, and the proportion infected with H. pylori was reduced to less than 10%. Since 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.
Ohta
T
T
Cancer Prevention Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, chuo-ku, Tokyo 104-0045, Japan.
Shibata
H
H
Kawamori
T
T
Iimuro
M
M
Sugimura
T
T
Wakabayashi
K
K
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005756:Gastritis / Q000188:drug therapy* / Q000209:etiology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D016480:Helicobacter pylori / Q000201:enzymology / Q000472:pathogenicity; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D016896:Treatment Outcome; D014510:Urease / Q000037:antagonists & inhibitors*
D001549:Benzamides; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C006358:acetohydroxamic acid; C032764:flurofamide; D014510:Urease