Advertisement

Digestive Diseases and Sciences

, Volume 39, Issue 11, pp 2389–2397 | Cite as

Effect of taurohyodeoxycholic acid, a hydrophilic bile salt, on bile salt and biliary lipid secretion in the rat

  • Mario Angelico
  • Leonardo Baiocchi
  • Alessandra Nistri
  • Antonio Franchitto
  • Paola Della Guardia
  • Eugenio Gaudio
Pancreatic And Biliary Disordens

Abstract

Taurohyodeoxycholic acid is a natural 6α-hydroxylated bile acid with an apparent hydrophilicity intermediate between those of tauroursodeoxycholic and taurocholic acids. We investigated in the rat the hepatobiliary metabolism, choleretic properties, and biliary maximum secretory rate (SRmax) of taurohyodeoxycholic in comparison with these two bile salts. Each compound was infused intravenously, at a rate increased in a stepwise manner from 100 to 300 nmol/min/100 g body wt, in bile salt-depleted bile fistula rats. The three bile salts appeared rapidly starting with the infusion and increased to represent more than 95% of the total bile salts. No apparent biliary metabolites were formed. All the bile salts caused a dose-dependent increase in bile flow and biliary lipid output. The absolute increase in bile flow was lower in rats infused with taurohyodeoxycholic acid, yet the volume of bile formed per nanomole of secreted bile salt was 13.8 nl for taurohyodeoxycholic, 6.4 nl for tauroursodeoxycholic acid, and 10.9 nl for taurocholic. TheSRmax values were 1080, 3240, and 960 nmol/min/100 g, respectively. At all infusion rates, taurohyodeoxycholic acid caused a greater (P<0.001) secretion of biliary lecithin compared to the other bile salts. There were no significant differences in the biliary secretion of cholesterol and proteins. Electron microscopy showed the recruitment of vesicles and lamellar bodies around and within bile canaliculi. In conclusion, taurohyodeoxycholic promotes a biliary lecithin secretion greater than expected from physicochemical predictions, representing a novel secretory property with potential pharmacological relevance.

Key words

taurohyodeoxycholic acid 6α-hydroxylation bile flow biliary lipid secretion bile-fistula rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Haslewood GAD: The Biological Importance of Bile Salts. North Holland Publishing, Amsterdam, 1978, pp 108–118Google Scholar
  2. 2.
    Staggers JE, Frost SC, Wells MA: Studies on fat digestion, absorption, and transport in the suckling rat. III: Composition of bile and evidence for enterohepatic circulation of bile salts. J Lipid Res 23:1143–1151, 1982Google Scholar
  3. 3.
    Almè BA, Bremmelgaard A, Sjovall J, Thomasse P: Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatography-mass spectrometry. J Lipid Res 18:339–362, 1977Google Scholar
  4. 4.
    Back P, Walter K: Developmental pattern of bile acid metabolism as revealed by bile acid analysis in meconium. Gastroenterology 78:671–676, 1980Google Scholar
  5. 5.
    Radominska-Pyrek, Zimniak P, Irshaid YM, Lester R, Tephly TR, Pyrek JS: Glucuronidation of 6-alfa-hydroxy bile acids by human liver microsomes. J Clin Invest 80:234–241, 1987Google Scholar
  6. 6.
    Haslewood GAD: Hyocholic acid, a trihydroxy bile acid from pig bile. Biochem J 56:38–39, 1954Google Scholar
  7. 7.
    Armstrong MJ, Carey MC: The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities. J Lipid Res 23:79–80, 1982Google Scholar
  8. 8.
    McSherry CK, Mosbach EH, Cohen BI, Une M, Stenger RJ, Singhal AK: Hyodeoxycholic acid: A new approach to gallstone prevention. Am J Surg 149:126–132, 1985Google Scholar
  9. 9.
    Dam H, Prange I, Sondergaard E: Alimentary production of gallstones in hamsters. 24. Influence of orally ingested chenodeoxycholic acid and hyodeoxycholic acid on formation of gallstones. Z Ernahrungswiss 11:80–94, 1972Google Scholar
  10. 10.
    Singhal AK, Cohen BI, Finver-Sadowsky J, McSherry CK, Mosbach EW: Role of hydrophilic bile acids and of sterols on cholelithiasis in the hamster. J Lipid Res 25:564–570, 1984Google Scholar
  11. 11.
    Cohen BI, Mosbach EW, McSherry CK, Stenger RJ, Kuroki S, Rzigalinski B: Gallstone prevention in prairie dogs: Comparison of chow vs semisynthetic diets. Hepatology 6:874–880, 1986Google Scholar
  12. 12.
    Angelico M, Mogavero L, Baiocchi L, La Rosa T, Gandin C: Taurohyodeoxycholate dissolves human cholesterol gallstones faster than the other taurine conjugates. Gastroenterology 100:A308, 1990Google Scholar
  13. 13.
    Johnstone CG, Irvin JL: The biliary excretion of various bile acids by patients with choledochostomy drainage, and the effect of oral administration of dessicated bile of the ox and the hog. Surgery 15:802–814, 1947Google Scholar
  14. 14.
    Thistle JL, Shoenfield LJ: Induced alterations in composition of bile of persons having cholelithiasis. Gastroenterology 61:488–496, 1971Google Scholar
  15. 15.
    Sacquet E, Parquet M, Riottot M, Raizman A, Jarrige A, Huguet C, Infante R: Intestinal absorption, excretion, and biotransformation of hyodeoxycholic acid in man. J Lipid Res 24:604–613, 1983Google Scholar
  16. 16.
    Small DM, Admirand W: Solubility of bile salts. Nature 221:265–267, 1969Google Scholar
  17. 17.
    Angelico M, Alvaro D, Cantafora A, Masella R, Gaudio E, Gandin C, Ginanni Corradini S, Ariosto F, Riggio O, Capocaccia L: Impaired handling and processing of lysophosphatidylcholine in rats with liver cirrhosis. Gastroenterology 101:228–237, 1991Google Scholar
  18. 18.
    Hardison WGM, Hatoff DE, Miyai K, Weiner RG: Nature of bile acid maximum secretory rate in the rat. Am J Physiol 241:G337-G343, 1981Google Scholar
  19. 19.
    Kitani K, Kanai S, Ohta M, Sato Y: Differing transport maxima values for taurine-conjugated bile salts in rats and hamsters. Am J Physiol 251:G852-G858, 1986Google Scholar
  20. 20.
    Cantafora A, Di Biase A, Alvaro D, Angelico M: An improved method for measuring the glycine and taurine conjugates of bile salts by high performance liquid chromatography with tauro-7alpha, 12alpha-dihydroxy-5beta-cholanic acid as internal standard. J Chromatogr 386:367–370, 1987Google Scholar
  21. 21.
    Takayama M, Itoh S, Nagasaki T, Tanimazu I: A new enzymatic method for serum choline-containing phospholipids. Clin Chim Acta 79:93–98, 1977Google Scholar
  22. 22.
    Cantafora A, Di Biase A, Alvaro D, Angelico M, Marin M, Attili AF: High performance liquid chromatography analysis of molecular species of phosphatidylcholine: Development of quantitative assay and its application to human bile. Clin Chim Acta 134:281–295, 1983Google Scholar
  23. 23.
    Siedel J, Hagele EO, Ziegenhorm J, Wahlefeld AW: Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 29:1075–1080, 1983Google Scholar
  24. 24.
    Carey MC: Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res 19:924–928, 1978Google Scholar
  25. 25.
    Cohen BI, Mosbach EH, Kuroki S, McSherry CK: Dissolution of cholesterol gallstones by bile acids in the prairie dog. Lipids 23:220–224, 1988Google Scholar
  26. 26.
    Cohen BI, Mosbach EW, McSherry CK, Rzigalinski B, Kuroki S: A hydrophilic bile acid effects partial dissolution of cholesterol gallstones in the prairie dog. Lipids 21:575–579, 1986Google Scholar
  27. 27.
    Angelico M, Avella A: Nuovi sali biliari all'orizzonte nella terapia medica della calcolosi biliare: Prospettiva di impiego dell'acido tauroiodesossicolico. Epatologia 34:151–159, 1988Google Scholar
  28. 28.
    Kitani K, Kanai S: Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats. Jpn J Physiol 35:443–462, 1985Google Scholar
  29. 29.
    Wheeler HO: Biliary excretion of bile acids, lecithin, and cholesterol in hamsters with gallstones. Gastroenterology 65:92–103, 1973Google Scholar
  30. 30.
    Salvioli G, Igimi H, Carey MC: Cholesterol gallstone dissolution in bile. Dissolution kinetics of crystalline cholesterol monohydrate by conjugated chenodeoxycholate-lecithin and conjugated ursodeoxycholate-lecithin mixtures: Dissimilar phase equilibria and dissolution mechanisms. J Lipid Res 24:701–720, 1983Google Scholar
  31. 31.
    Jones AL, Schmucker DL, Mooney JS, Adler RD, Ockner R: Alterations in hepatic pericanalicular cytoplasm during enhanced bile secretory activity. J Lab Invest 73:833–851, 1979Google Scholar
  32. 32.
    Hayakawa T, Ng OC, Ma A, Boyer JL: Taurocholate stimulates transcytotic vesicular pathways labeled by horseradish peroxidase in the isolated rat liver. Gastroenterology 99:216–222, 1990Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Mario Angelico
    • 1
    • 2
    • 3
    • 4
  • Leonardo Baiocchi
    • 1
    • 2
    • 3
    • 4
  • Alessandra Nistri
    • 1
    • 2
    • 3
    • 4
  • Antonio Franchitto
    • 1
    • 2
    • 3
    • 4
  • Paola Della Guardia
    • 1
    • 2
    • 3
    • 4
  • Eugenio Gaudio
    • 1
    • 2
    • 3
    • 4
  1. 1.From the Chair of GastroenterologyUniversity of CataniaCataniaItaly
  2. 2.Department of Public HealthUniversity of Tor VergataRomeItaly
  3. 3.2nd Division of GastroenterologyUniversity La SapienzaRome
  4. 4.Department of Experimental MedicineUniversity of L'AquilaAquilaItaly

Personalised recommendations