Planta Med 2000; 66(5): 429-434
DOI: 10.1055/s-2000-8584
Original Paper
Georg Thieme Verlag Stuttgart · New York

Influence of Curcumin on Cyclosporin-Induced Reduction of Biliary Bilirubin and Cholesterol Excretion and on Biliary Excretion of Cyclosporin and its Metabolites

Michael Deters1,*, Claudia Siegers2 , Wolfram Hänsel2 , Klaus-Peter Schneider3 , Gerhard Hennighausen4
  • 1 Institute of Pharmacology, Medical School Hannover, Hannover, Germany
  • 2 Pharmaceutical Institute, University of Kiel, Kiel, Germany
  • 3 Institute of Clinical Chemistry/Pathobiochemistry, University of Rostock, Rostock, Germany
  • 4 Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, Rostock, Germany
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
31. Dezember 2000 (online)

Abstract

We investigated the ability of curcumin, which can be extracted from different Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion, and its influence on biliary excretion of cyclosporin (CS) and its metabolites in the bile fistula model in rats. I.v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile flow (30 μl/kg/min) up to 200 %, biliary bilirubin excretion (3000 pmol/kg/min) up to 150 %, and biliary cholesterol excretion (22 nmol/kg/min) up to 113 %. CS (30 mg/kg) reduced bile flow to 66 % and biliary excretion of bilirubin and of cholesterol to 33 % of the basal value 30 min after i.v. injection. I.v. administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow dose dependently again to 130 % for 1 hour and biliary excretion of cholesterol and of bilirubin to 100 % of the basal value for 30 and 150 min, respectively. Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excretion, however, was not prevented by curcumin. Finally, the biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightly reduced by curcumin at a dose of 50 mg/kg (to 83 % of the initial values). The clinical importance of these controversial effects remains to be shown.

References

  • 1 Queneau  P E,, Bertault-Peres  P,, Mesdjian  E,, Durand  A,, Montet  J C.. Transplantation. 1993;;  56 530-4
  • 2 Queneau  P E,, Bertault-Peres  P,, Guitaoui  M,, Mesdjian  E,, Durand  A,, Montet  J C.. Digestive Diseases and Sciences. 1994;;  39 1581-5
  • 3 Barnes  D,, Talenti  D,, Cammell  G,, Goormastic  M,, Farquhar  L,, Henderson  M,, Vogt  D,, Mayes  J,, Westveer  M K,, Carey  W.. Hepatology. 1997;;  26 853-7
  • 4 Deters  M,, Siegers  C,, Muhl  P,, Hänsel  W.. Planta Medica. 1999;;  65 610-3
  • 5 Wahlefeld  A WG,, Herz  G,, Bernt  E.. Scand. J. clin. Lab. Invest.. 1972;;  29 Abstract 11-12
  • 6 Siedel  J,, Hagele  E O,, Ziegenhorn  J,, Wahlefeld  A W.. Clin. Chem.. 1983;;  29 1075-80
  • 7 Kahan  B D.. New Engl. J. Med.. 1989;;  321 1725-38
  • 8 Le Thai  B,, Dumont  M,, Michel  A,, Erlinger  S,, Houssin  D.. Transplantation. 1988;;  46 510-2
  • 9 Moslen  M T.. The Basic Science of Poisons. In: Klaasen CD, Amdur MO, Doull J, editors Casarett and Doull's Toxicology, 5th ed., New York:; McGraw-Hill, 1996: p. 403
  • 10 Stacey  N H,, Kotecka  B.. Gastroenterology. 1988;;  95 780-6
  • 11 Mosley  R H,, Johnson  T R,, Morrissette  J M.. J. Pharmacol. Exp. Ther.. 1990;;  253 974-80
  • 12 Moran  D,, Gonzalez de Buitrago  J M,, Fernandez  E,, Galan  A I,, Munoz  M E,, Jimenez  R.. J. of Hepatol.. 1998;;  29 68-77
  • 13 Billing  B H,, Jansen  F H,, Bilton  E.. Quantitative Aspects of Structure and Function. In: Baumgartner G, Preisig R, editors The liver. Basel:; Karger, 1973: pp. 386-91
  • 14 Sieg  A,, Stiehl  A,, Heirwegh  K PM,, Fevery  J,, Raedsch  R,, Kommerell  B.. Hepatology. 1989;;  10 14-20
  • 15 Galan  A I,, Roman  I D,, Munoz  M F,, Cava  F,, Gonzalez-Buitrago  J M,, Esteller  A,, Jimenez  R.. Biochemical Pharmacology. 1991;;  44 1105-13
  • 16 Lanzini  A,, Northfield  T C.. Eur. J. Clin. Invest.. 1990;;  21 259-72
  • 17 Reuter  H D.. Therapeutikon, Sonderheft. 1991: 25-30
  • 18 Fevery  J,, Blankeart  N,, Leroy  P,, Michiels  R,, Heirgwegh  K PM.. Hepatology. 1983;;  3 177-83
  • 19 Soudamini  K K,, Unnikrishnan  M C,, Soni  K B,, Kuttan  R.. Indian J. Physiol. Pharmacol.. 1992;;  36 239-43
  • 20 Ranjan  D,, Johnston  T D,, Wu  G,, Elliott  L,, Bondada  S,, Nagabhushan  M.. Journal of Surgical Research. 1998;;  77 174-8

Dr. Michael Deters

Institut für Pharmakologie Zentrum Pharmakologie und Toxikologie Medizinische Hochschule Hannover

Carl-Neuberg-Str. 1

30625 Hannover

Germany

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