Effects of cyclosporine and corticosteroids on bile secretion in the rat.
In order to study their effects on the bile secretion, cyclosporine and methylprednisolone were injected intravenously into rats at a dose of 10 mg/kg b.w. for 30 min. Methylprednisolone had no effect on bile secretion. Cyclosporine led to transient intrahepatic cholestasis characterized by decreased bile flow as well as a decrease of bile salts and cholesterol in bile. Phospholipid levels were not affected. Liver biopsy showed no particular anomaly. These findings suggest that the observed cholestatic reaction may be due to impairment of the metabolism of cholesterol into bile salts or of the conjugation of bile salts rather than to disturbances in bile secretion. After liver transplantation in humans, cholestasis associated with acute rejection or nonspecific cholestasis cannot be attributed directly to the effect of cyclosporine. Cholestasis can be offset by administering taurocholate at a dose of 10 mumol/min/kg b.w. in order to maintain bile salt and phospholipid levels high enough to ensure proper "vectorization" of cholesterol to bile.
Chanussot
F
F
INSERM Unité 130, Marseille, France.
Botta-Fridlund
D
D
Lechene de la Porte
P
P
Sbarra
V
V
Portugal
H
H
Pauli
A M
AM
Hauton
J
J
Gauthier
A
A
Lafont
H
H
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects
D001647:Bile Acids and Salts; D010743:Phospholipids; D016572:Cyclosporine; D002784:Cholesterol; D008775:Methylprednisolone