Lack of benefit of ursodeoxycholic acid in drug-induced cholestasis in the rat.
The administration of ursodeoxycholic acid (UDCA) has been reported to improve cholestasis in patients with primary biliary cirrhosis or sclerosing cholangitis. In the present study, we tested the hypothesis that UDCA similarly might reduce cholestasis induced by drugs. Rats were treated with three different drugs reported to induce cholestasis: 17 alpha-ethynylestradiol, alpha-napthylisothiocyanate, and cyclosporine A. UDCA administration (0.4.g/day-1.k-1 before and during administration of the cholestatic drug) did not improve survival, food intake, or serum indicators of cholestasis in any of these three animal models of cholestasis. To the extent that drug-induced cholestasis in rats mimics the human situation, we conclude that UDCA probably will not be beneficial in drug-induced cholestasis in humans.
Hillstrom
J
J
Research Service, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417.
Duane
W C
WC
Eckfeldt
J H
JH
Furne
J
J
Levitt
M D
MD
D015058:1-Naphthylisothiocyanate / Q000633:toxicity; D000818:Animals; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy*; D016572:Cyclosporine / Q000633:toxicity; D004997:Ethinyl Estradiol / Q000633:toxicity; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D004997:Ethinyl Estradiol; D015058:1-Naphthylisothiocyanate; D014580:Ursodeoxycholic Acid; D016572:Cyclosporine