In vitro inhibition of Helicobacter pylori urease: biochemical and ultrastructural analysis.
Inhibition of H. pylori urease was studied by means of electron-microscopy and electrophoretic methods using different urease inhibitors, such as acetohydroxamic-acid (AHA), L-ascorbic acid (AsA), copper ions, a combination of L-ascorbic acid with copper ions and UV light. AHA in two different concentrations and AsA at a concentration of 0.1 mg ml-1 showed incomplete inhibition of H. pylori urease activity in our electrophoretic experiments. Only membrane-bound activity was inhibited with AHA but not the activity localized within the cytoplasma as demonstrated by electron-microscopy. AsA at a concentration of 0.5 mg ml-1 and the combination of copper ions (1 microgram ml-1) with AsA completely inhibited the urease activity as demonstrated by electron-microscopy and electrophoretic experiments. Cu2+ ions in high concentrations (100 micrograms ml-1) and UV light exposure for more than 4 h induced a complete disintegration of H. pylori. Electrophoresis showed no active protein after UV light exposure of 2 h. Different urease inhibitors tested in this study showed dose-dependent inhibitory effects on H. pylori urease in vitro.
Nilius
M
M
Department of Internal Medicine II, University of Ulm, Germany.
Bode
G
G
Lehnhardt
G
G
Malfertheiner
P
P
D001205:Ascorbic Acid / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006877:Hydroxamic Acids / Q000494:pharmacology; D008854:Microscopy, Electron; D014466:Ultraviolet Rays; D014510:Urease / Q000037:antagonists & inhibitors* / Q000528:radiation effects
D006877:Hydroxamic Acids; C006358:acetohydroxamic acid; D003300:Copper; D014510:Urease; D001205:Ascorbic Acid