Effect of chronic administration of cyclosporin A on hepatic uptake and biliary secretion of bromosulfophthalein in rat.
Cyclosporin A (CyA) decreases bile flow and bile salt secretion in the rat. The purpose of this study was to examine the influence of CyA on the hepatic transport of bromosulfophthalein (BSP). Male Sprague-Dawley rats were injected with CyA at the daily dose of 10 mg/kg (treated animals) or solvent (controls) during three weeks. Hepatic uptake of BSP (assessed by the plasma disappearance curve of the dye) and biliary secretion during infusions (95.5 and 178 nmol/min/100 g) were examined in both groups. Administration of CyA resulted in a decrease in both bile flow and BSP biliary secretion at the two infusion rates used. BSP plasma disappearance rate was significantly lower in treated animals than in controls. Conjugation of the dye was unaffected by CyA. There was no modification in ALT activity or in liver histology. These data show that chronic administration of CyA in rats decreases both hepatic uptake and biliary secretion of BSP. Thus, the inhibitory effect of CyA on biliary secretion is not limited to bile salts but also is observed with other cholephilic substances.
Cadranel
J F
JF
Unité de Recherches de Physiopathologie Hépatique INSERM U-24, Hôpital Beaujon, Clichy, France.
Dumont
M
M
Mesa
V A
VA
Degott
C
C
Touchard
D
D
Erlinger
S
S
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000494:pharmacology
D003524:Cyclosporins; D013448:Sulfobromophthalein; D013656:Taurocholic Acid