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Beneficial Effects of Glycocholic Acid (GCA) on Gut Mucosal Damage in Bile Duct Ligated Rats

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Abstract

In order to investigate the effect of bile acids on gastrointestinal inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral or colonic) or saline 1 h before ethanol challenge and twice daily for 3 days in the ileitis group, while GCA was given twice daily for 3 days in the colitis group. BDL reduced the macroscopic and microscopic damage scores in the ileitis group compared to sham operated group, while it had no significant effect on ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index and microscopic damage in colitis group compared to saline-treated groups, but had no effect in ileitis group. Both BDL and GCA administration in BDL group reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration in BDL group inhibited gastric acid output and volume. Our results suggest that oral or colonic administration of primary bile acids may be useful for the treatment of gastrointestinal inflammations.

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References

  1. Garbutt, J. T., R. M. Wilkins, L. Lack, and M. P. Tyor. 1970. Bacterial modification of taurocholate during enterohepatic recirculation in normal man and patients with small intestinal disease. Gastroenterology 59:553–566.

    Google Scholar 

  2. Brodie, D. A., P. G. Cook, B. J. Bauer, and G. E. Dagle. 1970. Indomethacin-induced intestinal lesions in the rat. Toxicol. Appl. Pharmacol. 17:615–624.

    Google Scholar 

  3. Kent, T. H., R. M. Cardelli, and F. W. Stamler. 1969. Small intestinal ulcers and intestinal flora in rats given indomethacin. Am. J. Pathol. 54:237–245.

    Google Scholar 

  4. Robert, A. and T. Asano. 1977. Resistance of germ free rats to indomethacin-induced intestinal lesions. Prostaglandins 14:333–341.

    Google Scholar 

  5. Wax, J., W. A. Clinger, P. Varner, P. Bass, and C. V. Winder. 1970. Relationship of the enterohepatic cycle to ulcerogenesis in the rat small bowel with flufenamic acid. Gastroenterology 58:772–780.

    Google Scholar 

  6. Deitch, E. A., K. Sittig, M. Li, R. Berg, and R. D. Specian. 1987. Obstructive jaundice promotes bacterial translocation from the gut. Am. J. Surg. 159:79–84.

    Google Scholar 

  7. Runkel, N. S., F. G. Moody, G. S. Smith, L. F. Rodriguez, M. T. Larocco, and T. A. Miller. 1991. The role of the gut in the development of sepsis in acute pancreatitis. J. Surg. Res. 51:18–23.

    Google Scholar 

  8. Yamada, T., E. A. Deitch, R. D. Specian, M. A. Perry, R. B. Sartor, and M. B. Grisham. 1993. Mechanisms of acute and chronic intestinal injury induced by indomethacin. Inflammation 17:641–662.

    Google Scholar 

  9. Davies, G. R., M. E. Wilkie, and D. S. Rampton. 1993. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Dig. Dis. Sci. 38:417–425.

    Google Scholar 

  10. Utili, R., C. O. Abernathy, and H. J. Zimmerman. 1976. Cholestatic effects of Escherichia Coli endotoxin on the isolated perfused rat liver. Gastroenterology 70:248–253.

    Google Scholar 

  11. Auer, I. O., O. Roder, F. Wensinck, and J. P. van de Merwe. 1983. Selected bacterial antibodies in Crohn's disease and ulcerative colitis. Scand. J. Gastroenterol. 18:217–223.

    Google Scholar 

  12. Tanida, N., Y. Hikasa, M. Dodo, K. Sawada, A. Kawaura, and T. Shimoyama. 1986. High concentration and retained amidation of fecal bile acids in patients with active ulcerative colitis. Gastroenterol. Jpn. 21:245–254.

    Google Scholar 

  13. Ejderhamn, J. and B. Strandvik. 1991. Serum bile acids in relation to disease activity and intake of dietary fibers in juvenile ulcerative colitis. Digestion 50:162–169.

    Google Scholar 

  14. Floch, M. H., H. J. Binder, B. Filburn, and W. Gershengoren. 1972. The effect of bile acids on intestinal microflora. Am. J. Clin. Nutr. 25:1418–1426.

    Google Scholar 

  15. Sung, J. Y., E. A. Shaffer, K. Lam, I. Rususka, and J. W. Costerton. 1994. Hydrophobic bile salt inhibits bacterial adhesion on biliary stent material. Dig. Dis. Sci. 39:999–1006.

    Google Scholar 

  16. Cahill, C. J., J. A. Pain, and M. E. Bailey. 1990. Bile salts, endotoxin, and renal function in obstructive jaundice. Surg. Gynecol. Obstet. 165:519–522.

    Google Scholar 

  17. Uchida A., T. Yamada, T. Hayakawa, and M. Hoshino. 1997. Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intestinal inflammation. Am. J. Physiol. 272 (Gastrointest. Liver Physiol. 5):G1249–G1257.

    Google Scholar 

  18. Kullmann, F., H. Arndt, V. Gross, J. Ruschoff, and J. Scholmerich. 1997. Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis. Eur. J. Gastroenterol. Hepatol. 9:1205–1211.

    Google Scholar 

  19. Güunal, Ö., C. Yegen, A. Ö. Aktan, R. Yalin, and B. C. Yegen. 1996. Gastric functions in portal hypertension: role of endothelin. Dig. Dis. Sci. 41:585–590.

    Google Scholar 

  20. Udassin, R., D. Eimarl, J. Schiffman, and Y. Haskel. 1994. Epidural anesthesia accelerates the recovery of post ischemic bowel motility in the rat. Anesthesiology 80:832–836.

    Google Scholar 

  21. Morris, G. P., P. L. Beck, M. S. Herridge, W. T. Depew, M. R. Szewcuk, and J. L. Wallace. 1989. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803.

    Google Scholar 

  22. Wallace, J. L., P. Braquet, G. C. Ibbotson, W. K. Macnoughton, and G. Cirino. 1989. Assessment of the role of platelet activating factor in an animal model of inflammatory bowel disease. J. Lipid Med. 1:13–23.

    Google Scholar 

  23. Gruy-Kapral, C., K. H. Little, J. S. Fordtran, T. L. Meziere, L. R. Hagey, and A. F. Hofmann. 1999. Conjugated bile acid replacement therapy for short-bowel syndrome. Gastroenterology 116:15–21.

    Google Scholar 

  24. Bradley, P. P., D. A. Priebat, R. D. Christerser, and G. Rothstein. 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol. 78:206–209.

    Google Scholar 

  25. Yamada, T., M. Hoshino, T. Hayakawa, Y. Kamiya, H. Ohhara, K. Mizuno, H. Yamada, T. Nakazawa, T. Inagaki, A. Uchida, M. Miyaji, and T. Takeuchi. 1996. Bile secretion in rats with indomethacin-induced intestinal inflammation. Am. J. Physiol. 270 (Gastrointest. Liver Physiol. 33):G804–G812.

    Google Scholar 

  26. Bjarnason, I., B. Fehilly, P. Smethurst, and A. J. Levi. 1991. Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man. Gut 32:275–277.

    Google Scholar 

  27. Somasundaram, S., H. Hayllar, S. Rafi, J. M. Wrigglesworth, A. J. S. Macpherson, and I. Bjarnason. 1995. The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis. Scand. J. Gastroenterol. 30:289–299.

    Google Scholar 

  28. Calmus, Y., B. Weill, Y. Ozier, C. Chereau, D. Houssin, and R. Poupon. 1992. Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse. Gastroenterology 103:617–621.

    Google Scholar 

  29. Mizumoto, S., K. Harada, S. Takano, A. Misumi, and M. Akagi. 1986. Mechanisms of acute gastric mucosal lesion accompanying obstructive jaundice-role of bile acids in plasma. Gastroenterol. Jpn. 21:6–16.

    Google Scholar 

  30. Rosoff, C. B., and H. Goldman. 1968. Effect of the intestinal bacterial flora on acute gastric ulceration. Gastroenterology 55:212–222.

    Google Scholar 

  31. Clements, W. D. B., P. Erwin, M. I. Halliday, R. G. Barclay, and B. J. Rowlands. 1993. Extrahepatic biliary obstruction promotes bacterial translocation. Am. J. Surg. 165:749–751.

    Google Scholar 

  32. Sasaki, I., H. Miyakawa, J. Kameyama, Y. Kamiyama, and T. Sato. 1986. Influence of obstructive jaundice on gastric ulcer, intragastric pH and potential difference in rats. Tohoku J. Exp. Med. 150:161–168.

    Google Scholar 

  33. Matsuo, T., I. Sasaki, Y. Kamiyama, H. Naitoh, Y. Funayama, M. Takahashi, K. Fukushima, and S. Matsuno. 1989. Taurocholateinduced gastric damage in rats with obstructive jaundice. Scand. J. Gastroenterol. 24(suppl. 162):83–86.

    Google Scholar 

  34. Yamada, T., S. Marshall, R. D. Specian, and M. B. Grisham. 1992. A comparative analysis of two models of colitis in rats. Gastroenterology 102:1524–1534.

    Google Scholar 

  35. Masclee, A., A. Tangerman, A. van Schaik, E. W. van der Hoek, and J. H. M. van Tongeren. 1989. Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Eur. J. Clin. Invest. 19:384–389.

    Google Scholar 

  36. Deschner, E. E., B. I. Cohen, and R. F. Raicht. 1981. Acute and chronic effect of dietary cholic acid on colonic epithelial cell proliferation. Digestion 21:290–296.

    Google Scholar 

  37. Chang, W. C., J. R. Lupton, W. Frolich, G. L. Schoeffler, M. L. Peterson, and X. Q. Chen. 1994. A very low intake of fat is required to decrease fecal bile acid concentrations in rats. J. Nutr. 124:181–187.

    Google Scholar 

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Authors and Affiliations

  1. School of Medicine, Department of Physiology, Marmara University, İstanbul, Turkey

    Berna K. Oktar, Mehmet Ali Gülpınar, İnci Alican & Berrak Ç. Yeğen

  2. School of Medicine, Department of Histology, Marmara University, İstanbul, Turkey

    Feriha Ercan

  3. School of Medicine, Department of General Surgery, Marmara University, İstanbul, Turkey

    Asım Cingi

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  1. Berna K. Oktar
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  2. Mehmet Ali Gülpınar
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  5. İnci Alican
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  6. Berrak Ç. Yeğen
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Oktar, B.K., Gülpınar, M.A., Ercan, F. et al. Beneficial Effects of Glycocholic Acid (GCA) on Gut Mucosal Damage in Bile Duct Ligated Rats. Inflammation 25, 311–318 (2001). https://doi.org/10.1023/A:1012812616083

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