Pathogenic and therapeutic role of bile acids at reflux-gastritis

The aim of review. To present data on pathogenic significance of bile acids for upper regions of gastrointestinal tract (GIT) and to describe medical properties ursodeoxycholic acid (UDCA) at reflux-gastritis.

Summary. Reflux-gastritis is chemical type gastritis, morphologically manifested by foveolar hyperplasia, edema, proliferation of smooth-muscle fibres of lamina propria, insignificant chronic inflammation. There is evidences of relation of intestinal metaplasia to duodenogastric reflux (DGR). Bile acids at certain conditions possess damage effect on mucosa of the stomach and all GIT. They can increase endocellular concentration of calcium which is responsible for toxic effects of bile acids as a secondary messenger. Increase of endocellular calcium stimulates secretion of pepsinogen and acid production in the stomach,  that in the case of decreased cytoprotective factors by DGR can cause changes mucosal injury. According to the modern point of view bile acids are associated with a lot of neoplasms of digestive organs, including esophageal, stomach, small intestine, liver, pancreas and colorectal cancer. Exposition of bile acids results in formation of active forms of oxygen and nitrogen, damage of DNA, mutagenicity, induction of apoptosis in short-term prospect and resistance to apoptosis in long-term prospect. Gastric remnant gastritis is consideres to be a premalignant disease, thus bile acids play essential role in carcinogenesis. UDCA possesses choleretic effect and ability to displace toxic hydrophobic bile acids. It protects from oxydative stress, stabilizes cell membranes and inhibits apoptosis. At reflux-gastritis UDCA relieves clinical symptoms, improves of state of mucosa of the stomach and esophagus, and possess series of cytoprotective properties.

Conclusion. Prescription of UDCA is pathogenicly proved in patients with reflux-gastritis and gastroesopha geal reflux disease (GERD) with non-acidic refluxes. Cytoprotective and antiapoptotic effects of UDCA at reflux-gastritis are especially significant from the point of view of smoothing cancerogenic potential of bile acids.

1. Sobola G. M., O`Connor H.J., Dewar E. P., et al. Bile reflux and intestinal metaplasia in gastric mucosa. J Clin Pathol 1993; 46:235-40.

2. Vere C. C., Cazacu S., Comanescu V., Mogoanta L., Rogoveanu I., Ciurea T. Endoscopical and histological features in bile reflux gastritis. Rom J Morphol Embryol 2005; 46:269-74.

3. Chen S. L., Mo J. Z., Cao Z. J., Chen X. Y., Xiao S. D. Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis. World J Gastroenterol 2005; 11(18):2834-7.

4. Dixon M. F., Neville P. M., Mapstone N. P., et al. Bile reflux gastritis and Barrett’s esophagus: further evidence of a role for duodenogastroesophageal reflux? Gut 2001; 49:359-63.

5. Кайбышева В. О., Трухманов А. С., Сторонова О. А., Коньков М. Ю., Пономарев А. Б., Напалкова Н. Н., Нечаев В. М., Ивашкин В. Т. Морфофункциональные изменения в пищеводе при гастроэзофагеальной рефлюксной болезни в зависимости от характера рефлюктата. Клин перспективы гастроэнтерол гепатол 2014;(5):6.

6. Лапина Т. Л., Склянская О. А., Напалкова Н. Н., Картавенко И. М., Белятко Е. А., Подымова С. Д., Ивашкин В. Т. Пищевод Баррета после гастрэктомии: патогенетическое значение желчного рефлюкса. Рос журн гастроэнтерол гепатол колопроктол 2009; 19(4):75-8.

7. Dixon M. F., Genta R. M., Yardley J. H., Correa P., et al. Classification and grading of gastritis. The updated Sydney System. Am J Surg Pathol 1996; 20(10):1161-81.

8. Картавенко И. М., Лапина Т. Л., Коньков М. Ю., Склянская О. А., Копривица Н. Б., Ивашкин В. Т. Морфофункциональная оценка двенадцатиперстной кишки у больных с функциональной диспепсией. Рос журн гастроэнтерол гепатол колопроктол 2008; 18(5):23-32.

9. Matsuhisa T., Arakawa T., Watanabe T., Tokutomi T., Sakurai K., Okamura S., et al. Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases. Dig Endosc 2013; 25(5):519-25.

10. O’Connor H.J., Wyatt J. I., Dixon M. F., Axon A. T. Campylobacter like organisms and reflux gastritis. J Clin Pathol 1986; 39:531-4.

11. Park S., Chun H. J. Helicobacter pylori infection following partial gastrectomy for gastric cancer World J Gastroenterol 2014; 20(11):2765-70.

12. Li X. В., Lu H., Chen H. M., Chen X. Y., Ge Z. Z. Role of bile reflux and Helicobacter pylori infection on inflammation of gastric remnant after distal gastrectomy. J Dig Dis 2008; 9(4):208-12.

13. Aprea G., Canfora A., Ferronetti A., Giugliano A., Guida F., Braun A., et al. Morpho-functional gastric preand post-operative changes in elderly patients undergoing laparoscopic cholecystectomy for gallstone related disease. BMC Surg 2012; 12(Suppl 1):5.

14. Баранская Е. К., Ивашкин В. Т. Клинический спектр предраковой патологии желудка. Рос журн гастроэнтерол гепатол колопроктол 2002; 12(3):7-14.

15. Sitarz R., Maciejewski R., Polkowski W. P., Offerhaus G. Gastroenterostoma after Billroth antrectomy as a premalignant condition. World J Gastroenterol 2012; 18(25):3201-6.

16. Tersmette A. C., Offerhaus G. J., Tersmette K. W., Giardiello F. M., Moore G. W., Tytgat G. N., Vandenbroucke J. P. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions. Cancer Res 1990; 50:6486-9.

17. Northfield T. C., Hall C. N. Carcinoma of the gastric stump: risks and pathogenesis. Gut 1990; 31:1217-9.

18. Costarelli V. Bile acids as possible human carcinogens: new tricks from an old dog. Int J Food Sci Nutr 2009; 60(Suppl 6):116-25.

19. Bernstein H., Bernstein C., Payne C. M., Dvorak K. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol 2009; 15(27):3329-40.

20. Perez M. J., Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol 2009; 15(14):1677-89.

21. Keitel V., Kubitz R., Häussinger D. Endocrine and paracrine role of bile acids. World J Gastroenterol 2008; 14(37):5620-9.

22. Raufman J. P., Cheng K., Zimniak P. Activation of muscarinic receptor signaling by bile acids: physiological and medical implications. Dig Dis Sci 2003; 48:1431-44.

23. Stein H. J., Kauler W. K., Feussner H., Siewert J. R. Bile acids as component of the duodenogastric refluate: detection, relationship to bilirubin, mechanism of injury, and clinical relevance. Hepatogastroenterology 1999; 46:66-73.

24. Allen A., Flemström G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol 2005; 288:1-19.

25. Vang S., Longley K., Steer C. J., Low W. C. The unexpected uses of ursoand tauroursodeoxycholic acid in the treatment of non-liver diseases. Glob Adv Health Med 2014; 3(3):58-69.

26. Ratziu V. Treatment of NASH with ursodeoxycholic acid: pro. Clin Res Hepatol Gastroenterol 2012; 36(Suppl 1):41-5.

27. Thao T. D., Ryu H. C., Yoo S. H., Rhee D. K. Antibacterial and anti-atrophic effects of a highly soluble, acid stable UDCA formula in Helicobacter pylori-induced gastritis. Biochem Pharmacol 2008; 75(11):2135-46.

28. Stefaniwsky A. B., Tint G. S., Speck J., Shefer S., Salen G. Ursodeoxycholic acid treatment of bile reflux gastritis. Gastroenterology 1985; 89(5):1000-4.

29. Ozkaya M., Erten A., Sahin I., Engin B., Ciftçi A., Cakal E., et al. The effect of ursodeoxycholic acid treatment on epidermal growth factor in patients with bile reflux gastritis. Turk J Gastroenterol 2002; 13(4):198-202.

30. Dixon M. F., Mapstone N. P., Neville P. M., Moayyedi P., Axon A. T. Bile reflux gastritis and intestinal metaplasia at the cardia. Gut 2002; 51:351-5.

31. Nakos A., Zezos P., Liratzopoulos N., Efraimidou E., Manolas K., Moschos J., Molivas E., Kouklakis G. The significance of histological evidence of bile reflux gastropathy in patients with gastroesophageal reflux disease. Med Sci Monit 2009; 15(6):313-8.

32. Минушкин О. В., Масловский Л. В., Шулешова А. Г., Назаров Н. С. Лечение больных с рефлюкс-эзофагитом после гастрэктомии или резекции желудка. Клин перспективы гастроэнтерол гепатол 2013; 13(2):33-40.

33. Chen T. F., Yadav P. K., Wu R. J., Yu W. H., Liu C. Q., Lin H., Liu Z. J. Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux. World J Gastroenterol 2013; 19(14):2187-96.

34. Zhang Y., Yang X., Gu W., Shu X., Zhang T., Jiang M. Histological features of the gastric mucosa in children with primary bile reflux gastritis. World J Surg Oncol 2012; 10:27.