Choleretic effects of curcuminoids on an acute cyclosporin-induced cholestasis in the rat.
Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow in rats, whereas bisdemethoxycurcumin, which is mainly found in rhizomes of Curcuma longa, is believed to inhibit bile flow. To reevaluate this observation we investigated the influence of both curcuminoids on bile flow, bile acid concentration and excretion over a time period of 180 min in the bile fistula model in rats. Furthermore, we tested the ability of both curcuminoids to reduce cyclosporin-induced cholestasis. 30 min after intravenous injection of 25 mg/kg of curcumin and bisdemethoxycurcumin bile flow was enhanced from 500 microliters/kg/15 min (100%) to 180% and to 220%, respectively. The choleretic effect of bisdemethoxycurcumin lasted longer than that of curcumin. Following intravenous injection of 30 mg/kg of cyclosporin, which reduced bile flow, bile acid concentration (15 mmol/l) and excretion (12.5 mumol/kg/15 min) to 40% of the initial value, administration of curcumin and bisdemethoxycurcumin transiently increased bile flow to 100% and to 125% of the starting value, respectively. However, only bisdemethoxycurcumin statistically significantly attenuated cyclosporin-induced reduction of bile acid excretion. We conclude that the beneficial properties of curcuminoids for the therapy of cyclosporin-induced cholestasis still remain to be proven.
Deters
M
M
Institute of Experimental and Clinical Pharmacology and Toxicology, Rostock, Germany.
Siegers
C
C
Muhl
P
P
Hänsel
W
W
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy*; D003373:Coumaric Acids / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity; D036381:Diarylheptanoids; D007166:Immunosuppressive Agents / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002756:Cholagogues and Choleretics; D003373:Coumaric Acids; D036381:Diarylheptanoids; D007166:Immunosuppressive Agents; C034786:bisdemethoxycurcumin; D016572:Cyclosporine; D003474:Curcumin