The antacid Talcid adsorbs and neutralizes all proteins secreted by H. pylori including VacA cytotoxin: A new mechanism for its ulcer-healing action?

Background and Aim: Helicobacter pylori culture supernatant containing VacA cytotoxin significantly inhibits gastric cell proliferation and delays hea ling of experimental gastric ulcers. Since cell proliferation is crucial fo r ulcer healing, the removal of inhibitory effects of H. pylori secreted cy totoxin would have a beneficial effect on the healing process. In this stud y, we determined whether the antacid Talcid can adsorb, remove, or neutrali ze H. pylori derived VacA cytotoxin responsible for the above deleterious a ctions. Methods: Supernatants of viable H. pylori isogenic strains producin g VacA cytotoxin [VacA(+)] and with disrupted cytotoxin gene not producing cytotoxin [VacA(-)] were incubated with either placebo, Talcid 10 mg/ml, om eprazole 10 mg/ml (positive control) for 1-24 h. Treated supernatants were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to eva Iu ate proteins. We also studied the effect of supernatants on epiderm al growth factor stimulated Kato III cell proliferation using BrdU labelin g. Results: Talcid very effectively removed from the H. pylori culture supe rnatant the similar to 90 kD VacA(+) cytotoxin at 3 and 24 h (99.5% removal vs. placebo-treated control; p < 0.001). It also removed all other protein s, including 66-kD urease and 58-kD heat shock protein, secreted by both Va cA(+) and VacA(-) H. pylori strains. Omeprazole was completely ineffective in this regard. Preincubation with Talcid completely abolished the inhibito ry effect of VacA(+) H. pylori culture supernatant on epidermal growth fact or stimulated Kato ill cell proliferation. Conclusion: Adsorption and neutr alization by Talcid of all H. pylori secreted proteins may explain, at leas t in part, the ulcer-healing action of this drug.