Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion and on biliary excretion of cyclosporin and itsmetabolites

We investigated the ability of curcumin, which can be extracted from differ ent Curcuma species, to prevent cyclosporin-induced reduction of biliary bi lirubin and cholesterol excretion, and its influence on biliary excretion o f cyclosporin (CS) and its metabolites in the bile fistula model in rats. L v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-depe ndently basal bile flow (30 mu l/kg/min) up to 200 %. biliary bilirubin exc retion (3000 pmol/kg/min) Lip to 150%, and biliary cholesterol excretion (2 2 nmol/kg/min) up to 113%. CS (30 mg/kg) reduced bile flow to 66% and bilia ry 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 h our and biliary excretion of cholesterol and of bilirubin to 100 % of the b asal value for 30 and 150 min, respectively. Injection of curcumin 15 min b efore CS prevented the CS-induced drop of bile flow at 50 mg/kg and reducti on of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excre tion, however, was not prevented by curcumin. Finally, the biliary excretio ns of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightl y 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 show n.