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

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Abstract

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.

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Acknowledgments

This study was funded by Universiti Kebangsaan Malaysia with grant no. GGPM 2013-094. Special thanks to Dr. Alfizah Hanafiah (PPUKM) for providing the bacterial sample.

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Data generated or analyzed during this study was included in this article.

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Authors and Affiliations

  1. Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Noor Safwah Damanhuri, Endang Kumolosasi, Amirul Faiz Abd Razak & Ahmad Hasnan Mansor

  2. Quality Use of Medicine Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Marhanis Salihah Omar

Authors
  1. Noor Safwah Damanhuri
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  2. Endang Kumolosasi
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  3. Marhanis Salihah Omar
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  4. Amirul Faiz Abd Razak
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Contributions

EK and MSO planned the experimental phase and NSD and AHM performed the experiments and carried out the statistical analysis. EK and MSO conceptualized the study design and AFAR coordinated the research activities. The manuscript was written by NSD, MSO and reviewed by EK. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Endang Kumolosasi.

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Conflict of interest

The authors declared that they have no conflict of interest.

Ethical approval

The study was approved by Universiti Kebangsaan Malaysia Animal Ethics Committee, (UKMAEC) under the approval number FF/2015/ENDANG/29-SEPT./699-SEPT.-2015-SEPT in accordance with the international guidelines for animal studies (WHO Chronicle, 1985) [17].

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Damanhuri, N.S., Kumolosasi, E., Omar, M.S. et al. The influence of P-glycoprotein expression in the standard treatment of Helicobacter pylori infection in Sprague Dawley rats. DARU J Pharm Sci 29, 13–22 (2021). https://doi.org/10.1007/s40199-020-00377-2

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  • DOI: https://doi.org/10.1007/s40199-020-00377-2

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