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УЖМБС 2019, 4(2): 278–283
https://doi.org/10.26693/jmbs04.02.278
Biology

Influence of Prolonged Using of Proton Pump Blockers on the Stomach and Colon Microflora in Rats

Makarchuk V. V., Pylypenko S. V., Koval’ A. A.
Abstract

The purpose of this work was to assess the quantitative and qualitative composition of the microflora in the stomach and large intestine after 28 days of omeprazole and pantoprazole administration. Materials and methods. The studies were conducted on 30 white nonlinear probes-males weighing 160-180 g, which were randomized, divided into three groups of 10 animals in each. Manipulation with animals and their content in the university were carried out in accordance with international recommendations and national legislation on medical and biological research and confirmed the conclusion of the ethical committee of the Taras Shevchenko National University of Kyiv. The first (control) group included rats, which were injected 0.2 ml of water for 28 days intraperitoneally (i.p.). The rats of the second group were injected 14 mg / kg of omeprazole (manufactured by “Sigma-Aldrich”, USA) once daily for 28 days, which was dissolved in 0.2 ml of water for injection. Rats of the third group administered pantoprazole (OM) at a dose of 0.57 mg / kg once per day for 28 days (“Ulsepan” manufactured by “World Medicine”, UK), dissolved in 0.2 ml of water for injection. Results and discussion. The obtained results showed that qualitative and quantitative composition of stomach microflora was changed in both experimental groups after 28 days of suppression of HCl secretion in rats’ stomach by omeprazole and pantoprazole. The rate of sowing lactobacillus was significantly decreased. The concentration of Enterobacter increased in the first experimental group, but it was even lower in the second group than in control. The quantitative and qualitative indexes of rats, which were injected by pantoprazole during 28 days, did not differ from the control values of sowing of such representatives of the conditionally pathogenic microflora from the stomach, as Klebsiella, Proteus, Staphylococcus aureus at all, and Staphylococcus epidermidis almost. There was an imbalance between the parameters of the conditionally pathogenic and normal microflora of the rats’ intestine of both experimental groups. However, the concentration of such conditionally pathogenic microorganisms as Escherichia coli (hemolytic), Escherichia coli (with altered fermentative properties) in the second group was almost different from the control values. In this case, the indicators of Escherichia coli (lactose negative), Klebsiella, Staphylococcus epidermidis (with hemolysis) and the Candida species fungi were the same as in the control group. Conclusions. Suppression of gastric secretion of hydrochloric acid of the rats by omeprazole during 28 days led to the development of dysbiosis in the stomach and colon. Suppression of gastric secretion of hydrochloric acid of the rats by pantoprazole during 28 days to a lesser extent led to microbiological shifts in the stomach and colon compared to the group, which was administered omeprazole. Prospects for further research will deal with a study of quantitative and qualitative composition of microflora in the stomach and colon under the conditions of modeling of prolonged gastric hypochlorhydria by other blockers proton pumps, and the correction of this condition by various probiotic preparations.

Keywords: hypochlorhydria, omeprazole, pantoprazole, dysbiosis

Full text: PDF (Ukr) 208K

References
  1. Blyume KH, Donat F, Varnke A, Shuh BS. Farmakokynetycheskie lekarstvennye vzaymodeystvyya s uchastyem ingibitorov protonnoy pompy. Rus med zhurn. 2009; 17(9): 622-31. [Ukrainian]
  2. Bordin DS. Bezopasnost' lecheniya kak kriteriy vybora ingibitora protonnoy pompy bol'nomu gastroezofageeversual'noy reflyuksnoy bolezn'yu. Consilium Medicum. 2010; 12(8): 8-13. [Russian]
  3. Brandt Z. Statisticheskiye metody analiza nablyudeniy. M: Mir; 1975. 312 s. [Russian]
  4. Chernobrovyy VM, Ksenchyn OO. Pantoprazol: osoblyvosti farmakokinetyky, kyslotopryhnichuvalʹnoyi diyi, klinichnoyi efektyvnosti ta bezpechnosti zastosuvannya. Suchasna gastroenterologiya. 2016; 4(90): 60–6. [Ukrainian]
  5. Glants G. Mediko-biologicheskaya statistika. M: Praktika; 1999. 459 s. [Russian]
  6. Paliy I.H. Pantoprazol – inhibitor protonnoyi pompy z dovedenoyu perenosymistyu, bezpekoyu ta efektyvnistyu. Zdorov’ya Ukrayiny. 2013; 2013: 5-6. [Ukrainian]
  7. Ali Khan M, Howden CW. The Role of Proton Pump Inhibitors in the Management of Upper Gastrointestinal Disorders. Gastroenterol Hepatol (NY). 2018 Mar; 14(3): 169-75. https://www.ncbi.nlm.nih.gov/pubmed/29928161. https://www.ncbi.nlm.nih.gov/pmc/articles/6004044
  8. Bartle HJ, Harkins MJ. The gastric secretion: its bactericidal value to man. Amer J Med Sci. 1925; 169: 377-88. https://doi.org/10.1097/00000441-192503000-00008
  9. Bekkers CH, Touw DJ, Lamers CB, Geus WP. The effect of CYP2C19 polymorphism on the pharmacokinetics and acidinhibitory effects of oral lansoprazole and omeprazole. Br J Clin Pharmacol. 2002; 54(5): 553.
  10. Garrod LP. A study on the bactericidal power of hydrochloric acid and of gastric juice. St Burt Hosp Rep. 1939; 72: 145-67.
  11. Gashi Z, Bahtiri E, Gashi A, Sherifi F. Proton Pump Inhibitors Diminish Barrett’s Esophagus Length: Our Experience. Open Access Maced J Med Sci. 2018; 6(6): 1041–5. https://www.ncbi.nlm.nih.gov/pubmed/29983798. https://www.ncbi.nlm.nih.gov/pmc/articles/6026409. https://doi.org/10.3889/oamjms.2018.232
  12. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, et al. An unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor ADMA. Ciculation. 2013 Aug 20; 128(8): 845-53. https://www.ncbi.nlm.nih.gov/pubmed/23825361. https://www.ncbi.nlm.nih.gov/pmc/articles/3838201. https://doi.org/10.1161/circulationaha.113.003602
  13. Howden CW, Hunt RH. Relationship between gastric secretion and infection. Gut. 1987; 28(1): 96-107. https://www.ncbi.nlm.nih.gov/pubmed/3546004. https://www.ncbi.nlm.nih.gov/pmc/articles/1432731. https://doi.org/10.1136/gut.28.1.96
  14. Huang JQ, Hunt RH. Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician. Best Pract Res Clin Gastroenterol. 2001; 15(3): 355-70. https://www.ncbi.nlm.nih.gov/pubmed/11403532. https://doi.org/10.1053/bega.2001.0184
  15. Mukherjee S, Jana T, Pan JJ. Adverse Effects of Proton Pump Inhibitors on Platelet Count: A Case Report and Review of the Literature. Case Rep Gastrointest Med. 2018 Apr 30; 2018: 4294805. https://www.ncbi.nlm.nih.gov/pubmed/29854491. https://www.ncbi.nlm.nih.gov/pmc/articles/5952557. https://doi.org/10.1155/2018/4294805
  16. Mullin GM, Gabello M, Murray LJ, Farrell CP, Bellows J, Wolov KR, et al. Proton pump inhibitors: actions and reactions. Drug Disc Today. 2009; 14(13-14): 647-60. https://www.ncbi.nlm.nih.gov/pubmed/19443264. https://doi.org/10.1016/j.drudis.2009.03.014
  17. Prewett EJ, Hudson M, Nwokolo ChU, Sawyerr AM, Pounder RE. Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole. Gastroenterology. 1991; 100: 873-7. https://doi.org/10.1016/0016-5085(91)90258-M
  18. Radhofer-Welte S. Pharmacokinetics and metabolism of the proton pump inhibitor pantoprasole in man. Drugs today. 1999; 35(10): 765-72. https://www.ncbi.nlm.nih.gov/pubmed/12973371. https://doi.org/10.1358/dot.1999.35.10.561695
  19. Scarpignato C, Gatta L, Zullo A, Blandizzi C. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016; 14(1): 179. https://www.ncbi.nlm.nih.gov/pubmed/27825371. https://www.ncbi.nlm.nih.gov/pmc/articles/5101793. https://doi.org/10.1186/s12916-016-0718-z
  20. Stockbrugger RW, Cotton PB, Eugenides N, Bartholomew BA, Hill MJ, Walters CL. Intragastric nitrites, nitrates, and bacterial overgrowth during cimetidine treatment. Gut. 1982; 23: 1048-54. https://www.ncbi.nlm.nih.gov/pubmed/7173716. https://www.ncbi.nlm.nih.gov/pmc/articles/1419839. https://doi.org/10.1136/gut.23.12.1048
  21. Thorens J, Froehlich F, Schwizer W, Saraga E, Bille J, Gyr K, et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomized double blind study. Gut. 1996; 39(1): 54-9. https://www.ncbi.nlm.nih.gov/pubmed/8881809. https://www.ncbi.nlm.nih.gov/pmc/articles/1383231. https://doi.org/10.1136/gut.39.1.54