Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion and on biliary excretion of cyclosporin and its metabolites.
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 microliters/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.
Deters
M
M
Institute of Pharmacology, Medical School Hannover, Germany. Deters.Michael@MH-Hannover.de
Siegers
C
C
Hänsel
W
W
Schneider
K P
KP
Hennighausen
G
G
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000737:chemistry / Q000494:pharmacology*; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002784:Cholesterol / Q000378:metabolism*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D016572:Cyclosporine / Q000009:adverse effects* / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002756:Cholagogues and Choleretics; D016572:Cyclosporine; D002784:Cholesterol; D003474:Curcumin; D001663:Bilirubin