The influence of P-glycoprotein expression in the standard treatment of Helicobacter pylori infection in Sprague Dawley rats.

BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic. OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen. METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively. RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p < 0.05) in P-gp expression level and a more severe ulcer formation compared to the healthy rats. The ulcer developed at different levels in the rats with inhibited, induced, or normal P-gp expression. After receiving the standard therapy for H. pylori, it was observed that the healing rate for ulcer was increased to 91% (rats with inhibited P-gp expression), 82% (rats with induced P-gp expression) and 75% in rats with normal P-gp. The use of rifampicin to induce P-gp level was also shown to be effective in eradicating the H. pylori infection. CONCLUSION: The synergism in the standard therapy by using two antibiotics (clarithromycin and amoxicillin) and proton pump inhibitor (omeprazole) have shown to effectively eradicate the H. pylori infection. Thus, P-gp expression influenced the effectiveness of the treatment.

Influences of proton pump inhibitor on Helicobacter pylori adherence to the gastrointestinal cell lines.

BACKGROUND/AIMS: Helicobacter pylori is a carcinogenic bacterium that could induce P-glycoprotein expression in the human gastrointestinal tract. Bacterial adherence to the gastrointestinal cell lines could be influenced by the level of P-glycoprotein. This study aimed to determine the influence of proton pump inhibitors that exhibit an inhibitory effect on P-glycoprotein in gastrointestinal carcinoma cell lines, namely Caco-2 and LS174T, in relation to H. pylori adherence. MATERIALS AND METHODS: Caco-2 and LS174T cells lines treated with omeprazole and esomeprazole were used in this study to assess the bacterial attachment of H. pylori within certain incubation periods. RESULTS: The presence of proton pump inhibitors increased the H. pylori adherence in a time-dependent manner in both Caco-2 and LS174T cell lines. The double inhibition of P-glycoprotein using proton pump inhibitor and P-glycoprotein inhibitor caused low P-glycoprotein expression in the cell lines, resulting in higher H. pylori adherence compared to the control cell lines. CONCLUSION: Proton pump inhibitors may alter P-glycoprotein expression in the gastrointestinal tract, and subsequently H. pylori adherence on the cell lines, and may contribute to resistance to drug therapy.