Editorial Type:
Physiology

Bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge

Toshiaki Kakimoto Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Search for other papers by Toshiaki Kakimoto in
Current site
Google Scholar
PubMed Close
 DVM
,
Hideyuki Kanemoto Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Search for other papers by Hideyuki Kanemoto in
Current site
Google Scholar
PubMed Close
 DVM, PhD
,
Kenjiro Fukushima Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Search for other papers by Kenjiro Fukushima in
Current site
Google Scholar
PubMed Close
 DVM
,
Koichi Ohno Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Search for other papers by Koichi Ohno in
Current site
Google Scholar
PubMed Close
 DVM, PhD
, and
Hajime Tsujimoto Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Search for other papers by Hajime Tsujimoto in
Current site
Google Scholar
PubMed Close
 DVM, PhD
DOI:
https://doi.org/10.2460/ajvr.78.2.223
Volume/Issue:
Volume 78: Issue 2
Online Publication Date:
01 Feb 2017
Restricted access
Sign In Reprints and Permissions Purchase Article

Abstract

OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge.

ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group).

PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group.

RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.

Abstract

OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge.

ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group).

PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group.

RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.

Contributor Notes

Address correspondence to Dr. Ohno (aohno@mail.ecc.u-tokyo.ac.jp).

Drs. Kakimoto and Kanemoto contributed equally to the manuscript.

Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Feb 2017

  • 1. Besso JG, Wrigley RH, Gliatto JM, et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladder mucocele. Vet Radiol Ultrasound 2000; 41: 261–271.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 2. Pike FS, Berg J, King NW, et al. Gallbladder mucocele in dogs: 30 cases (2000–2002). J Am Vet Med Assoc 2004; 224: 1615–1622.

  • 3. Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland Sheepdogs: 38 cases (1995–2005). J Am Vet Med Assoc 2007; 231: 79–88.

  • 4. Kutsunai M, Kanemoto H, Fukushima K, et al. The association between gall bladder mucoceles and hyperlipidaemia in dogs: a retrospective case control study. Vet J 2014; 199: 76–79.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 5. Mesich ML, Mayhew PD, Paek M, et al. Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. J Small Anim Pract 2009; 50: 630–635.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 6. Tsukagoshi T, Ohno K, Tsukamoto A, et al. Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele. Vet Radiol Ultrasound 2012; 53: 84–91.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 7. Kovatch RM, Hilderbrandt PK, Marcus LC. Cystic mucinous hypertrophy of the mucosa of the gall bladder in the dog. Pathol Vet 1965; 2: 574–584.

  • 8. Worley DR, Hottinger HA, Lawrence HJ. Surgical management of gallbladder mucoceles in dogs: 22 cases (1999–2003). J Am Vet Med Assoc 2004; 225: 1418–1422.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 9. Kesimer M, Cullen J, Cao R, et al. Excess secretion of gel-forming mucins and associated innate defense proteins with defective mucin un-packaging underpin gallbladder mucocele formation in dogs. PLoS One 2015; 10: e0138988.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 10. Klinkspoor JH, Kuver R, Savard CE, et al. Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells. Gastroenterology 1995; 109: 264–274.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 11. Englert E, Harman CG, Freston JW, et al. Studies on the pathogenesis of diet-induced dog gallstones. Am J Dig Dis 1977; 22: 305–314.

  • 12. Kook PH, Schellenberg S, Rentsch KM, et al. Effect of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs. Am J Vet Res 2011; 72: 1607–1612.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 13. Xiao ZL, Rho AK, Biancani P, et al. Effects of bile acids on the muscle functions of guinea pig gallbladder. Am J Physiol Gastrointest Liver Physiol 2002; 283: G87–G94.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 14. Choi M, Moschetta A, Bookout AL, et al. Identification of a hormonal basis for gallbladder filling. Nat Med 2006; 12: 1253–1255.

  • 15. Thomas C, Pellicciari R, Pruzanski M, et al. Targeting bile-acid signalling for metabolic diseases. Nat Rev Drug Discov 2008; 7: 678–693.

  • 16. Washizu T, Ishida T, Washizu M, et al. Changes in bile acid composition of serum and gallbladder bile in bile duct ligated dogs. J Vet Med Sci 1994; 56: 299–303.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 17. Malek S, Sinclair E, Hosgood G, et al. Clinical findings and prognostic factors for dogs undergoing cholecystectomy for gall bladder mucocele. Vet Surg 2013; 42: 418–426.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 18. Ji S, Jung S, Kim B, et al. Feasibility of percutaneous contrast ultrasound-guided cholecystography in dogs. Vet Radiol Ultrasound 2015; 56: 296–300.

  • 19. Okuyama S, Kokubun N, Higashidate S, et al. A new analytical method of individual bile acids using high performance liquid chromatography and immobilized 3α-hydroxysteroid dehydrogenase in column form. Chem Lett 1979; 12: 1443–1446.

    • Search Google Scholar
    • Export Citation

  • 20. Dray-Charier N, Paul A, Combettes L, et al. Regulation of mucin secretion in human gallbladder epithelial cells: predominant role of calcium and protein kinase C. Gastroenterology 1997; 112: 978–990.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 21. Klinkspoor JH, Yoshida T, Lee SP. Bile salts stimulate mucin secretion by cultured dog gallbladder epithelial cells independent of their detergent effect. Biochem J 1998; 332: 257–262.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 22. Lavoie B, Balemba OB, Godfrey C, et al. Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels. J Physiol 2010; 588: 3295–3305.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 23. Beaver MH, Wostmann BS, Madsen DC. Bile acids in bile of germfree and conventional dogs. Proc Soc Exp Biol Med 1978; 157: 386–389.

  • 24. Keitel V, Cupisti K, Ullmer C, et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology 2009; 50: 861–870.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 25. Han SI, Studer E, Gupta S, et al. Bile acids enhance the activity of the insulin receptor and glycogen synthase in primary rodent hepatocytes. Hepatology 2004; 39: 456–463.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 26. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439: 484–489.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

  • 27. Zhang Y, Edwards PA. FXR signaling in metabolic disease. FEBS Lett 2008; 582: 10–18.

  • 28. Duboc H, Taché Y, Hofmann AF. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis 2014; 46: 302–312.

  • 29. Kobelska-Dubiel N, Klincewicz B, Cichy W. Liver disease in cystic fibrosis. Prz Gastroenterol 2014; 9: 136–141.

  • 30. Washizu T, Tomoda I, Kaneko JJ. Serum bile acid composition of the dog, cow, horse and human. J Vet Med Sci 1991; 53: 81–86.

  • 31. Uno T, Okamoto K, Onaka T, et al. Hourly changes of total bile acids and conjugated bile acid fractions in the serum before and after meals, and compositional ratio of conjugated bile acid fractions from the serum and the gallbladder in healthy dogs. J Anim Clin Med 2007; 16: 125–128.

    • Search Google Scholar
    • Export Citation

Advertisement