Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori.
We have recently shown that Helicobacter pylori possesses marked alcohol dehydrogenase (ADH) activity and is capable--when incubated with an ethanol containing solution in vitro--of producing large amounts of acetaldehyde. In the present study we report that some drugs commonly used for the eradication of H. pylori and for the treatment of gastroduodenal diseases are potent ADH inhibitors and, consequently, effectively prevent bacterial oxidation of ethanol to acetaldehyde. Colloidal bismuth subcitrate (CBS), already at a concentration of 0.01 mM, inhibited H. pylori ADH by 93% at 0.5 M ethanol and decreased oxidation of 22 mM ethanol to acetaldehyde to 82% of control. At concentrations above 5 mM, CBS almost totally inhibited acetaldehyde formation. Omeprazole, a drug also known to suppress growth of H. pylori, also inhibited H. pylori ADH and suppressed bacterial acetaldehyde formation significantly to 69% of control at a drug concentration of 0.1 mM. By contrast, the H2-receptor antagonists ranitidine and famotidine showed only modest effect on bacterial ADH and acetaldehyde production. We suggest that inhibition of bacterial ADH and a consequent suppression of acetaldehyde production from endogenous or exogenous ethanol may be a novel mechanism by which CBS and omeprazole exert their effect both on the growth of H. pylori as well as on H. pylori associated gastric injury.
Roine
R P
RP
Research Unit of Alcohol Diseases, University of Helsinki, Finland.
Salmela
K S
KS
Höök-Nikanne
J
J
Kosunen
T U
TU
Salaspuro
M
M
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001729:Bismuth / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde; C002791:bismuth tripotassium dicitrate; D009853:Omeprazole; D001729:Bismuth