The antacid Talcid adsorbs and neutralizes all proteins secreted by H. pylori including VacA cytotoxin: a new mechanism for its ulcer-healing action?
OBJECTIVE
Helicobacter pylori culture supernatant containing VacA cytotoxin significantly inhibits gastric cell proliferation and delays healing of experimental gastric ulcers. Since cell proliferation is crucial for ulcer healing, the removal of inhibitory effects of H. pylori secreted cytotoxin would have a beneficial effect on the healing process. In this study, we determined whether the antacid Talcid can adsorb, remove, or neutralize H. pylori derived VacA cytotoxin responsible for the above deleterious actions.


METHODS
Supernatants of viable H. pylori isogenic strains producing VacA cytotoxin [VacA(+)] and with disrupted cytotoxin gene not producing cytotoxin [VacA(-)] were incubated with either placebo, Talcid 10 mg/ml, omeprazole 10 mg/ml (positive control) for 1-24 h. Treated supernatants were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate proteins. We also studied the effect of supernatants on epidermal growth factor stimulated Kato III cell proliferation using BrdU labeling.


RESULTS
Talcid very effectively removed from the H. pylori culture supernatant the approximately 90 kD VacA(+) cytotoxin at 3 and 24 h (99.5% removal vs. placebo-treated control; p<0.001). It also removed all other proteins, including 66-kD urease and 58-kD heat shock protein, secreted by both VacA(+) and VacA(-) H. pylori strains. Omeprazole was completely ineffective in this regard. Preincubation with Talcid completely abolished the inhibitory effect of VacA(+) H. pylori culture supernatant on epidermal growth factor stimulated Kato III cell proliferation.


CONCLUSIONS
Adsorption and neutralization by Talcid of all H. pylori secreted proteins may explain, at least in part, the ulcer-healing action of this drug.
Tarnawski
A
A
Veterans Administration Medical Center, Long Beach, Calif. 90822, USA. atarnawski@pop.long-beach.va.gov
Pai
R
R
Itani
R
R
Wyle
F A
FA
D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000704:Analysis of Variance; D000863:Antacids / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D016480:Helicobacter pylori / Q000378:metabolism*; D008276:Magnesium Hydroxide / Q000494:pharmacology*
D000863:Antacids; D001426:Bacterial Proteins; D003603:Cytotoxins; C010467:hydrotalcite; D000536:Aluminum Hydroxide; D008276:Magnesium Hydroxide