Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat.
Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.
Deters
Michael
M
Institute of Pharmacology, Medical School Hannover, Hannover, Germany. Michael.Deters@solvay.com
Klabunde
Til
T
Meyer
Hartmut
H
Resch
Klaus
K
Kaever
Volkhard
V
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000097:blood; D001658:Biliary Fistula; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy; D002784:Cholesterol / Q000097:blood; D030024:Curcuma; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016572:Cyclosporine / Q000378:metabolism / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D000960:Hypolipidemic Agents; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D003474:Curcumin