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Adaptive hepatic changes in mild stenosis of the common bile duct in the rat

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Research in Experimental Medicine

Abstract

Adaptive hepatic changes were investigated in rats with mild stenosis of the common bile duct and in sham-operated controls. The studies were performed 24 h and 7–12 days postoperatively. A continuous intravenous infusion of taurocholic acid at stepwise-increasing rates was performed to explore the responses to bile acid effects. During the infusion, bile flow and the outputs of bile acids, phospholipids, cholesterol, alkaline phosphatase and gamma glutamyl transpeptidase were studied. At the end of the infusion, hepatic morphometric measurements were performed. In other experimental sets, biliary excretions of horseradish peroxidase, a marker of microtubule-dependent vesicular transport in the hepatocyte, and sulphobromophthalein, a well-known organic anion model, were studied. In other rats, bile acid pool size and composition were determined by depletion of bile. The results in rats with mild stenosis maintained for 24 h showed a greater susceptibility to the toxicity of taurocholic acid, as revealed by the abrupt decrement in bile flow at high rates of infusion, and increased outputs of phospholipids and canalicular enzymes. Conversely, rats with mild stenosis maintained for 7–12 days showed decreased bile acid maximum secretory rate and biliary outputs of phospholipids and canalicular enzymes, as well as hepatocyte hypertrophy. These findings may explain the limited hepatic and systemic repercussion of experimental mild stenosis of the common bile duct and help us to understand the early stages of constriction of the common bile duct in man.

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References

  1. Accatino L, Hono J, Maldonado M, Icarte MA, Persico R (1988) Adaptive regulation of hepatic bile salt transport. Effect of prolonged bile salt depletion in the rat. J Hepatol 7:215–223

    Article  CAS  PubMed  Google Scholar 

  2. Accatino L, Figueroa C, Pizarro M, Solis N (1995) Enhanced biliary excretion of canalicular membrane enzymes in estrogen-induced and obstructive cholestasis, and effects of different bile acids in the isolated perfused rat liver. J Hepatol 22:658–670

    Article  CAS  PubMed  Google Scholar 

  3. Accatino L, Pizarro M, Solís N, Koenig CS, Vollrath V, Cianale J (1996) Modulation of hepatic content and biliary excretion of P-glycoproteins in hepatocellular and obstructive cholestasis in the rat. J Hepatol 25:349–361

    Article  CAS  PubMed  Google Scholar 

  4. Adler RD, Wannagat FJ, Ockner RK (1977) Bile secretion in selective biliary obstruction. Adaptation of taurocholate transport maximum to increased secretory load in the rat. Gastroenterology 73:129–136

    CAS  PubMed  Google Scholar 

  5. Angelini G, Sgarbi D, Castagnini P, Cavallini G, Bovo P (1994) Common bile duct involvement in chronic pancreatitis. Ital J Gastroenterol 26:79–82

    CAS  PubMed  Google Scholar 

  6. Aronson DC, Chamuleau RAFM, Frederiks WM, Gooszen HG, Heijmans HSA, James J (1993) Reversibility of cholestatic changes following experimental common bile duct obstruction: fact or fantasy? J Hepatol 18:85–95

    Article  CAS  PubMed  Google Scholar 

  7. Arrese, M, Pizarro M, Solís N, Accatino L (1997) Adaptive regulation of hepatic bile salt transport: role of bile salt hydrophobicity and microtubule-dependent vesicular pathway. J Hepatol 26:694–702

    Article  CAS  PubMed  Google Scholar 

  8. Baak JPA, Oort J, Bouw GM, Stolte LAM (1977) Quantitative morphology: methods and materials. I Stereology and norphometry. Eur J Obstet Gynecol Reprod Biol 7:45–52

    Google Scholar 

  9. Baginski ES, Foa PP, Zak B (1967) Microdetermination of inorganic phosphate, phospholipids and total phosphate in biological materials. Clin Chem 13:323–332

    Google Scholar 

  10. Berthelot P, Erlinger S, Dhumeaux D, Preaux AM (1970) Mechanism of phenobarbital induced hypercholeresis in the rat. Am J Physiol 219:809–813

    CAS  PubMed  Google Scholar 

  11. Binnet JL (1977) La citologie quantitative, 1st edn. Press Univ France, Vendome

    Google Scholar 

  12. Bulle F, Mavier P, Zafrani ES, et al (1990) Mechanism of γ-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach. Hepatology 11:545–550

    Article  CAS  PubMed  Google Scholar 

  13. Buscher HP, Mitenberger C, MacNelly S, Gerok W (1989) The histoautoradiographic localization of taurocholate in rat liver after bile duct ligation. Evidence for ongoing secretion and reabsorption processes. J Hepatol 8:181–191

    Article  CAS  PubMed  Google Scholar 

  14. Coleman R, Rahman K (1992) Lipid flow in bile formation. Biochim Biophys Acta 1125:113–133

    Article  CAS  PubMed  Google Scholar 

  15. De Hoff R, Rhines F (1972) Microscopie quantitative, 2nd edn. Masson et Cie, Paris

    Google Scholar 

  16. Desmet VJ (1992) Modulation of the liver in cholestasis. J Gastroenterol Hepatol 7:313–323

    Article  CAS  PubMed  Google Scholar 

  17. Desmet V, Roskams, Van Eyken P (1995) Ductular reactions in the liver. Pathol Res Pract 191:513–524

    Article  CAS  PubMed  Google Scholar 

  18. Elías H (1955) Liver morphology. Biol Rev 30:263–310

    Article  Google Scholar 

  19. Erlinger S (1996) New insights into the mechanism of hepatic transport and bile secretion. J Gastroenterol Hepatol 11:575–579

    Article  CAS  PubMed  Google Scholar 

  20. Forker EL, Gibson G (1973) Interaction between sulfobromophthalein (BSP) and taurocholate. In: Paumgartner G, Preisig R (eds) The liver, quantitative aspects of structure and function. Karger, Basel, pp 326–336

    Google Scholar 

  21. Frezza EE, Gerunda GE, Piebani A, et al (1993) Effect of ursodeoxycholic acid administration on bile duct proliferation and cholestasis in bile duct ligated rat. Dig Dis Sci 38:1291–1296

    Article  CAS  PubMed  Google Scholar 

  22. González MC, Sutherland E, Simon FR (1979) Regulation of hepatic transport of bile salt. Effect of protein synthesis inhibition on excretion of bile salts and binding to liver surface membrane fractions. J Clin Invest 63:684–694

    Article  PubMed Central  PubMed  Google Scholar 

  23. Gregus Z, Fischer E, Varga F (1979) Effect of sodium taurocholate on the hepatic transport of brosulphthalein in rats. Arch Int Pharmacodyn Ther 238:124–133

    CAS  PubMed  Google Scholar 

  24. Hardison WGM, Hatoff DE, Miyai K, Weiner RG (1981) Nature of bile acid maximum secretory rate in the rat. Am J Physiol 241:G337–G343

    CAS  PubMed  Google Scholar 

  25. Hatoff DE, Hardison GM (1981) Bile acids modify alkaline phosphatase induction and bile secretion pressure after bile duct obstruction in the rat. Gastroenterology 80:666–672

    CAS  PubMed  Google Scholar 

  26. Häussinger D, Wettstein M, Warkulat U, Dahl S von, Noé B, Schliess F (1997) Cell volume signalling, osmolytes and liver function. Digestion 58[suppl 1]:21–23

    Article  PubMed  Google Scholar 

  27. Hirano N, Tazuma S, Kajiyama G (1997) Transcytotic vesicle fusion with canalicular membranes is modulated by phospholipid species: implications for biliary lipid secretion. J Gastroenterol Hepatol 12:534–539

    Article  CAS  PubMed  Google Scholar 

  28. Hofmann AF (1997) Biliary secretion: future perspectives. Digestion 58[suppl 1]:24–28

    Article  PubMed  Google Scholar 

  29. Icarte MA, Pizarro M, Accatino L (1991) Adaptive regulation of hepatic bile salt transport: effects of alloxan diabetes in the rat. Hepatology 14:671–678

    CAS  PubMed  Google Scholar 

  30. Jansen PLM, Peters WHM, Meijer DKJ (1987) Hepatobiliary excretion of organic anions in double-mutant rats with a combination of defective canalicular transport and uridine 5′-diphosphate-glucuronyltransferase deficiency. Gastroenterology 93:1094–1103

    CAS  PubMed  Google Scholar 

  31. Kubota K, Bandai Y, Watanabe M, Toyoda H, Oka T, Makuuchi M (1996) Biliary stricture due to mucosal hyperplasia of the common bile duct: a case report. Hepaton Gastroenteroly 43:147–151

    CAS  Google Scholar 

  32. Kuipers F, Havinga R, Bosschieter H, Toorop GP, Hindriks FR, Vonk RJ (1985) Enterohepatic circulation in the rat. Gastroenterology 88:403–411

    CAS  PubMed  Google Scholar 

  33. Lesur G, Levy Ph, Flejou JS, Belghiti F, Fekete P, Bernades P (1993) Factors predictive of liver histopathological appearance in chronic alcoholic pancreatitis with common bile duct stenosis and increased serum alkaline phosphatase. Hepatology 18:1078–1081

    Article  CAS  PubMed  Google Scholar 

  34. Lowe PJ, Kan KS, Barnwell SG, Sharma RK, Coleman R (1985) Transcytosis and paracellular movements of horseradish peroxidase across liver parenchymal tissue from blood to bile. Effect of α-naphthylisothiocyanate and colchicine. Biochem J 229:529–537

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Marinelli RA, Peñalva GL (1992) Effects of lysosomotropic agents on the taurocholate-stimulated biliary excretion of horseradish peroxidase. Biochem Pharmacol 44:1683–1686

    Article  CAS  PubMed  Google Scholar 

  36. Mills PR, Meier PJ, Smith DJ, Ballatori N, Boyer JL, Gordon ER (1987) The effects of changes in the fluid state of rat liver plasma membrane on the transport of taurocholate. Hepatology 7:61–66

    Article  CAS  PubMed  Google Scholar 

  37. Oude Elferink RPJ, Frijters CMG, Paulusma C, Groen AK (1996) Regulation of canalicular transport activities. J Hepatol 24[Suppl 1]:94–99

    CAS  PubMed  Google Scholar 

  38. Oude Elferink RPJ, Tytgat GNJ, Groen AK (1997) The role of mdr2 P-glycoprotein in hepatobiliary lipid transport. FASEB J 11:19–28

    Google Scholar 

  39. Paumgartner G, Sauter K, Schwarz HP, et al (1973) Hepatic excretory transport maximum for free and conjugated cholate in the rat. In: Paumgartner G, Preisig R (eds) The liver. Quantitative aspects of structure and function. Karger, Basel, pp 337–343

    Google Scholar 

  40. Rioux F, Perea A, Yousef IM, et al (1994) Short-term feeding of a diet enriched in phospholipids increases bile formation and the bile acid transport maximum in rats. Biochim Biophys Acta 1214:193–202

    Article  CAS  PubMed  Google Scholar 

  41. Rodriguez-Garay EA, Agüero RM, Pisani G, Trbojevich RA, Farroni A, Viglianco RA (1996) Rat model of mild stenosis of the common bile duct. Res Exp Med 196:105–116

    Article  CAS  Google Scholar 

  42. Roma MG, Peñalva GL, Agüero RM, Rodriguez-Garay EA (1994) Hepatic transport of organic anions in taurolithocholate-induced cholestasis in rats. J Hepatol 20:603–610

    Article  CAS  PubMed  Google Scholar 

  43. Song JY, Van Noorden CJF, Frederiks WM (1997) Alterations of hepatocellular inter-mediate filaments during extrahepatic cholestasis in rat liver. Virchows Arch 430:253–260

    Article  CAS  PubMed  Google Scholar 

  44. Stiehl A, Rudolph G, Sauer P, et al (1997) Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenosis in primary sclerosing cholangitis. J Hepatol 26:560–566

    Article  CAS  PubMed  Google Scholar 

  45. Suchy FJ, Sippel CJ, Ananthanarayanan M (1997) Bile acid transport across the hepatocyte canalicular membrane. FASEB J 11:109–205

    Google Scholar 

  46. Talalay P (1960) Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:119–143

    Article  CAS  PubMed  Google Scholar 

  47. Tavoloni N (1987) The intrahepatic biliary epithelium: an area of growing interest in hepatology. Semin Liver Dis 7:280–292

    Article  CAS  PubMed  Google Scholar 

  48. Teschke R, Koch T (1986) Biliary excretion of gamma-glutamyltransferase. Selective enhancement by acute ethanol administration. Biochem Pharmacol 35:2521–2525

    CAS  Google Scholar 

  49. Tietz PS, Thiestle JL, Miller LJ, La Russo NF (1984) Development and validation of a method for measuring the glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography. J Chromatogr 336:249–257

    Article  CAS  PubMed  Google Scholar 

  50. Weibel E (1963) Principles and methods for the morphometric study of the lung and other organs. Lab Invest 12:131–155

    CAS  PubMed  Google Scholar 

  51. Weibel E, G]’omez D (1962) A principle for counting tissue structures on random sections. J Appl Physiol 17:343–348

    CAS  PubMed  Google Scholar 

  52. Weibel E, Stäubli W, Gnägi H, Hess F (1969) Correlated morphometric and biochemical studies on the liver cell. I Morphometric model, stereologic methods and normal morphometric data for rat liver. J Cell Biol 469–491

  53. Wielandt AM, Pizarro M, Solis N, Arrese M, Accatino L (1993) Postcholestatic alka-line phosphatase activity after relief of bile duct obstruction in the rat. Hepatology 18:179–187

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Emilio A. Rodriguez-Garay.

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Rodriguez-Garay, E.A., Larocca, C., Pisani, G. et al. Adaptive hepatic changes in mild stenosis of the common bile duct in the rat. Res. Exp. Med. 198, 307–323 (1998). https://doi.org/10.1007/s004330050114

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  • DOI: https://doi.org/10.1007/s004330050114

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